Showing papers in "Medical Science Monitor in 2005"

Lead toxicity update. A brief review.

Abstract: Lead is a metal which has been associated with human activities for the last 6000 years. In ancient civilizations, uses of lead included the manufacture of kitchen utensils, trays, and other decorative articles. However, lead is also toxic to humans, with the most deleterious effects on the hemopoietic, nervous, reproductive systems and the urinary tract. The main sources of lead exposure are paints, water, food, dust, soil, kitchen utensils, and leaded gasoline. The majority of cases of lead poisoning are due to oral ingestion and absorption through the gut. Lead poisoning in adults occurs more frequently during exposure in the workplace and primarily involves the central nervous system. Symptoms of hemopoietic system involvement include microcytic, hypochromic anemia with basophilic stippling of the erythrocytes. Hyperactivity, anorexia, decreased play activity, low intelligence quotient, and poor school performance have been observed in children with high lead levels. Lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity, and low birth weight. In 1991, the Centers for Disease Control and Prevention in the USA redefined elevated blood lead levels as those > or = 10 microg/dl and recommended a new set of guidelines for the treatment of lead levels > or =15 microg/dl.

Rapid stress reduction and anxiolysis among distressed women as a consequence of a three-month intensive yoga program.

Abstract: Summary Background: Emotional distress is an increasing public health problem and Hatha yoga has been claimed to induce stress reduction and empowerment in practicing subjects. We aimed to evaluate potential effects of Iyengar Hatha yoga on perceived stress and associated psychological outcomes in mentally distressed women. Material/Methods: A controlled prospective non-randomized study was conducted in 24 self-referred female subjects (mean age 37.9±7.3 years) who perceived themselves as emotionally distressed. Subjects were offered participation in one of two subsequential 3-months yoga programs. Group 1 (n=16) participated in the fi rst class, group 2 (n=8) served as a waiting list control. During the yoga course, subjects attended two-weekly 90-min Iyengar yoga classes. Outcome was assessed on entry and after 3 months by Cohen Perceived Stress Scale, State-Trait Anxiety Inventory, Profi le of Mood States, CESD-Depression Scale, Bf-S/Bf-S’ Well-Being Scales, Freiburg Complaint List and ratings of physical well-being. Salivary cortisol levels were measured before and after an evening yoga class in a second sample. Results: Compared to waiting-list, women who participated in the yoga-training demonstrated pronounced and signifi cant improvements in perceived stress (P<0.02), State and Trait Anxiety (P<0.02 and P<0.01, respectively), well-being (P<0.01), vigor (P<0.02), fatigue (P<0.02) and depression (P<0.05). Physical well-being also increased (P<0.01), and those subjects suffering from headache or back pain reported marked pain relief. Salivary cortisol decreased signifi cantly after participation in a yoga class (P<0.05). Conclusions: Women suffering from mental distress participating in a 3-month Iyengar yoga class show significant improvements on measures of stress and psychological outcomes. Further investigation of yoga with respect to prevention and treatment of stress-related disease and of underlying mechanism is warranted.

Vectors and delivery systems in gene therapy

Abstract: Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and, especially, molecular medicine is now changing the basics of clinical medicine. Reports of long-term side effects of the first successful human gene therapy study have slowed the penetration of DNA usage into clinical routine. However, the main safety problem lies in the secure and efficient delivery of genes into target cells and tissues. A number of older and more recently discovered techniques have been developed for therapeutic gene transfer. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy. The best known are viral vectors derived from adenoviruses and adeno-associated viruses. Specific properties of lentiviruses and retroviruses ensure their status in current gene therapy procedures. Recent advances in the preparation of lipoplexes and greater safety support the use of naked DNA transfer. The latest approach, using bacteria as vectors for gene therapy or as in situ producers of therapeutic proteins (alternative gene therapy), must undergo critical evaluation in further experiments.

Angiotensin II and vascular inflammation.

Abstract: Vascular inflammation is involved in the initiation and progression of atherosclerosis, and is also present in hypertension- and diabetes-induced vascular complications. Angiotensin II (Ang II), the key effector of the renin-angiotensin system (RAS), plays a central role in the regulation of blood pressure and electrolyte homeostasis. There is accumulating evidence to indicate that Ang II is also capable of inducing inflammatory response in the vascular wall. This review summarizes the current understanding of the molecular mechanisms and signal transduction pathways of Ang II-induced vascular inflammation. The roles of modulators of Ang II-induced inflammatory response, such as nitric oxide (NO), bradykinin, cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), and epoxyeicosatrienoic acids (EETs), are also discussed. The current data suggest that Ang II modifies several steps of inflammatory response, such as increase of vascular permeability, leukocyte infiltration, tissue hypertrophy/proliferation, and fibrosis. Ang II, via the type 1 (AT1) receptors, enhances the production of reactive oxygen species (ROS) through stimulation of NAD(P)H oxidase in the vascular wall. Increased oxidative stress contributes to endothelial dysfunction and to vascular inflammation by stimulating the redox-sensitive transcription factors (NF-kappaB) and by upregulating adhesion molecules, cytokines, and chemokines. The pro-inflammatory action of Ang II may help us to understand the molecular mechanisms of hypertension- and diabetes-induced vascular complication as well as the pleiotropic actions of drugs interfering with RAS.

Could mean platelet volume be a predictive marker for acute myocardial infarction

Abstract: Background: Platelets play an important role in developing intravascular thrombus, the major cause of acute coronary syndromes. We investigated the clinical value of mean platelet volume (MPV) in coronary atherosclerosisand its possibility of being an independent risk factor for acute myocardial infarction (MI). Material/Methods: Two hundred patients who underwent coronary angiography were included in the study. Thirty-five patients were randomly selected for each of the four study groups of stable (SAP) and unstable (USAP) angina pectoris and MI with and without ST-segment elevation. Sixty patients with chest pain having normal coronary angiograms were controls. The groups were compared regarding age, sex, smoking, diabetes, hypertension, positive family history, number of diseased vessels, lipid profile, complete blood count, creatin kinase (CK)-MB, Troponin-I, and MPV. Results: MPV was found to be elevated in MI patients compared with controls (p<0.001) and SAP (p<0.05) and patients with two- (p<0.001) and three-vessel (p<0.001) disease. We observed a significant association between MI and higher MPV (≥12 fl). High MPV (p<0.001) and WBC (p<0.001) were independent risk factors, among others. CK-MB, Troponin-I, and higher MPV demonstrate MI risk with 87%, 70%, and 87% specificity, respectively, while higher MPV only demonstrates coronary artery disease with 98% specificity. Conclusions: Our study shows high MPV is an independent risk factor for coronary atherosclerosis and MI. Because this is a simple, economic, and practical method, we suggest MPV be considered with other conventional risk factors.

Testosterone and aggressiveness.

Abstract: Aggressiveness is an ancestral behavior common to all animal species. Its neurophysiological mechanisms are similar in all vertebrates. Males are generally more aggressive than females. In this review, aggressive behavior in rodents, monkeys, and man and the role of testosterone and brain serotonin levels have been considered. Interspecific aggressiveness in rats has been studied considering the mouse-killing behavior; the neonatal androgenization of females increases adult mouse-killing as does the administration of testosterone in adults. Intraspecific aggressiveness was studied by putting two or more male rats (or mice) in the same cage; the condition of subjection or dominance is influenced by testosterone. In monkeys, testosterone is related to aggressiveness and dominance and, during the mating season, increases in testosterone levels and aggressive attitude are observed. In men, higher testosterone levels were obtained in perpetrators of violent crimes, in men from the army with antisocial behaviors, in subjects with impulsive behaviors, alcoholics and suicidals, in athletes using steroids, and during competitions. Aggressive and dominant behavior are distinguished. Testosterone influences both of these, even if man is usually inclined to affirm his power without causing physical damage. Testosterone receptors are mainly in some hypothalamic neurons, where it is aromatized into estrogens, which determine the increase in aggressiveness. A relation between testosterone levels and diencephalic serotonin has been shown: in fact, the lack of serotonin increases aggressive behaviors both in animals and man. Testosterone also increases ADH levels in the medial amygdala, lateral hypothalamus, and preoptical medial area, involved in aggressive behaviors.

Septic shock; current pathogenetic concepts from a clinical perspective.

Abstract: Sepsis is an infection-induced syndrome characterized by a generalized inflammatory state and represents a frequent complication in the surgical patient. The normal reaction to infection involves a series of complex immunologic processes. A potent, complex immunologic cascade ensures a prompt protective response to microbial invasion in humans. Although activation of the immune system during microbial invasion is generally protective, septic shock develops in a number of patients as a consequence of excessive or poorly regulated immune response to the offending organism (Gram-negative or Gram-positive bacteria, fungi, viruses, or microbial toxins). This unbalanced reaction may harm the host through a maladaptive release of endogenously generated inflammatory compounds. Many mechanisms are involved in the pathogenesis of septic shock, including the release of cytokines, the activation of neutrophils, monocytes, and microvascular endothelial cells, as well as the activation of neuroendocrine reflexes and plasma protein cascade systems, such as the complement system, the intrinsic (contact system) and extrinsic pathways of coagulation, and the fibrinolytic system. In critically ill patients, the gastrointestinal tract plays a central role in the pathogenesis of septic shock. The potential for complementary and synergistic interaction of the different components in this cascade highlights the difficulty encountered in trying to identify a single means of altering the progression of sepsis and septic shock to multiple organ dysfunction syndrome (MODS) and multiple organ failure (MOF).

Prevalence and trends of prehypertension and hypertension in United States: National Health and Nutrition Examination Surveys 1976 to 2000.

Abstract: Background: The Seventh Report of the Joint National Committee (JNC-7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provided a new classification of blood pressure for adults aged ≥18 years to guide screening and treatment efforts. Material/Methods: Using the new classification, we examined trends and prevalence of pre-hypertension (120-139/80-89 mm Hg), stage 1 hypertension (140-159/90-99 mm Hg), and stage 2 hypertension (≥160/100 mm Hg) in a nationally representative sample of the United States population. We analyzed 4115 adult persons from 1999 and 2000 National Health and Nutrition Examination Survey (NHANES), 20,322 persons from NHANES II (1976-1980) and 30,818 persons from NHANES III (1988-1992). Results: In the United States population aged 20 or greater, we found that an estimated 41.9 million men and 27.8 million women have pre-hypertension, 12.8 million men and 12.2 million women have stage 1 hypertension, and 4.1 million men and 6.9 million women have stage 2 hypertension. Age-and sex-adjusted rates of pre-hypertension increased among non-Hispanic White, African American, and Hispanic persons between 1988-1992 and 1999-2000. Age- and sex-adjusted rates of stage 1 hypertension increased among Hispanics between 1988-1992 and 1999-2000. Age- and sex-adjusted rates of stage 2 hypertension decreased among non-Hispanic Whites between 1988-1992 and 1999-2000, but were unchanged for African American and hispanic persons. Conclusions: With over a 100 million persons with pre-hypertension or hypertension in the United States, a renewed effort directed towards screening, education, and treatment is required, particularly in the Hispanic population.

Curcumin attenuates diet-induced hypercholesterolemia in rats.

Abstract: Background Curcumin (a component of turmeric) has long been used as a spice and food-coloring agent. In experimental animals, curcumin has shown anti-diabetic, anti-inflammatory, cytotoxic and anti-oxidant properties. Material/methods The possible hypolipidemic effect of curcumin was investigated in rats fed a high-cholesterol diet (HCD). The lipid profile and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed in serum, as well as anti-oxidant parameters in liver tissues. Results Feeding the animals a high cholesterol diet (HCD) for 7 consecutive days (1 ml 100 g(-1)) resulted in marked hypercholesterolemia, increased serum level of low-density lipoprotein cholesterol (LDL-C), but a decreased serum high-density lipoprotein cholesterol (HDL-C). Curcumin admixed with the diet (0.5% w/w) decreased serum total cholesterol (TC) by about 21% and LDL-C by 42.5%, but it increased serum HDL by 50%. The atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were reduced by 52% and 35%, respectively. Curcumin also decreased the enzyme activities of serum AST and ALT, which were increased in HCD animals. Conclusions Curcumin showed an obvious hypocholesterolemic effect that could be due to an effect on cholesterol absorption, degradation or elimination, but not due to an anti-oxidant mechanism. This could be supported by the finding in our study that neither HCD nor curcumin-admixed HCD had any effects on the liver content of glutathione (GSH) or superoxide dismutase (SOD) activity. Thus one could argue that ingestion of curcumin-containing spices in the diet, especially one rich in fats, could have a lipid-lowering effect.

Is angiotensin-II an endogenous pro-inflammatory molecule?

Abstract: Angiotensin-II, a product of angiotensin converting enzyme (ACE) action, regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NFkappaB, increases oxidant stress, and suppresses nitric oxide synthesis. Thus, angiotensin-II is pro-inflammatory in nature. Hence, increase in ACE activity and the concentrations of angiotensin-II initiate and perpetuate inflammation. Since ACE is present in many tissues including: the uterus, placenta, vascular tissue, heart, brain, adrenal cortex and kidney, leukocytes, alveolar macrophages, peripheral monocytes, neuronal cells and epididymal cells, this suggests that angiotensin-II may have a role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is known to play a significant role. This suggests that ACE inhibitors and/or angiotensin-II receptor blockers could be of significant benefit in the management of these conditions. Alternatively, structural analogues of presently available ACE inhibitors and angiotensin-II receptor blockers could be developed such that they are not only useful in the treatment of hypertension and CHF but also possess anti-inflammatory actions.

Dietary fats, fatty acids and insulin resistance: short review of a multifacetedconnection.

Abstract: Insulin resistance is a growing worldwide phenomenon, which progressively develops over years, and finally, if unchecked, predisposes to cardiovascular disease and diabetes mellitus type 2. Insulin resistance is a generalized metabolic disorder characterized by inefficient insulin function in skeletal muscle, liver and adipocytes. There is growing evidence that an increased free fatty acid level, and more importantly, the relative amounts of saturated and unsaturated fatty acids contributing to it, plays an important role in the development of insulin resistance. In turn, this is a reflection of the composition of dietary fat. Ultimately both the dietary intake and plasma levels determine the fatty acid composition of cell membranes. Higher levels of membrane saturated fatty acids seem to greatly impair the action of insulin, whereas the presence of polyunsaturated fatty acids, especially of the omega-3 and -6 families, in contrast, improves insulin sensitivity. In vitro studies, however, have not always corroborated the clinical evidence. Possible roles played by the various saturated and unsaturated fatty acids in the insulin-signaling pathway are discussed in light of recent evidence. Fatty acids have also been shown to alter gene expression in cells, in particular the peroxisome proliferator-activated receptor-gamma2 gene, adding to this multifaceted connection. As man has moved over the centuries from a hunter-gatherer diet to greater intakes of saturated and trans-fatty acids, insulin resistance has appeared with its related pathology. Greater understanding of the role played by dietary fat and plasma fatty acids in pathogenesis of insulin resistance, will allow for more timely prevention and improved treatment in the future.

Experiences with three different fiber supplements in weight reduction.

Abstract: Background: Fiber supplements added to a caloric diet have additional effects on weight reduction in overweight subjects. The aim of this study was to compare the effect of various commercial fiber supplements (glucomannan, guar gum and alginate) on weight reduction in healthy overweight subjects. Material/methods: One hundred and seventy six men and women were included to receive either active fiber substance or placebo in randomized placebo-controlled studies. The fiber supplements consisted of the viscous fibers glucomannan (Chrombalance), glucomannan and guar gum (Appe-Trim) and glucomannan, guar gum and alginat (Glucosahl). Results: All fiber supplements plus a balanced 1200 kcal diet induced significantly weight reduction more than placebo and diet alone, during a five week observation period. However, there were no significant differences between the different fibers in their ability to induce weight reduction, which was approximately 0.8 kg/week (3.8 +/- 0.9, 4.4 +/- 2.0, 4.1 +/- 0.6 in the Chrombalance, Appe-Trim and Glucosahl group, respectively). Conclusions: Glucomannan induced body weight reduction in healthy overweight subjects, whereas the addition of guar gum and alginate did not seem to cause additional loss of weight.

Clinical spectrum and critical care management of Posterior Reversible Encephalopathy Syndrome (PRES).

Abstract: Background Posterior Reversible Encephalopathy (PRES) is characterized by acute-onset headache, altered mental status, cortical blindness and seizures, with parietal-occipital involvement. We report all cases of PRES diagnosed in our intensive care unit during the last 4 years, and evaluate their outcome in terms of the different medical treatments used. Even if usually reversible, PRES can sometimes result in death or irreversible neurological deficit, such as chronic epilepsy. Material/methods From January 2001 to January 2005, we identified 8 female patients with PRES. All patients underwent basal and follow-up brain MRI. Patients referred to Epilepsy Center (about 3000 patients) were reviewed in order to identify subjects with a clinical history of PRES. These latter were clinically re-evaluated and underwent video-EEG, MRI study and neuropsychological testing. Results Of the 8 patients, 5 had hypertensive encephalopathy during pregnancy; 2 had eclampsia during the postpartum period; 1 patient with chronic renal failure developed symptoms after immunosuppressive treatment. In all patients but 1, neurological and radiological abnormalities resolved after appropriate treatment. In addition, we found 2 patients with temporal lobe epilepsy subsequent to a previous PRES. MRI revealed cortical-subcortical malacia in the parietal-occipital regions. Conclusions The widespread use of MRI technology has made PRES familiar to many clinicians. Although PRES is reversible when treatment is instituted, delayed diagnosis and therapy can result in chronic neurological sequelae. The relationship between hypertensive encephalopathy and chronic epilepsy needs to be confirmed by longitudinal studies. Normalization of blood pressure and treatment of seizures deserves particular attention.

Apoptosis in liver diseases--detection and therapeutic applications.

Abstract: The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. Amongst the hepatitis viruses, only hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. Of the different antiviral defense systems employed by the tissue, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Loss of tolerance to the liver autoantigens may result in autoimmune hepatitis (AIH). This review outlines the recent findings that highlight the role and mechanisms of apoptotic processes in the course of liver diseases. Among factors that contribute to liver pathology, we discuss the role of tumor necrosis factor (TNF)-alpha, HBx, ds-PKR, TRAIL, FasL, and IL-1alpha. Since TNF and FasL-induced hepatocyte apoptosis is implicated in a wide range of liver diseases, including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure, these items will be discussed in greater detail in this review. We also highlight some recent discoveries that pave the way for the development of new therapeutic strategies by protecting hepatocytes (for example by employing Bcl-2, Bcl-XL or A1/Bfl-1, IAPs, or synthetic caspase inhibitors), or by the induction of apoptosis in stellate cells. The assessment of the severity of liver disease, as well as monitoring of patients with chronic liver disease, remains a major challenge in clinical hepatology practice. Therefore, a separate chapter is devoted to a novel cytochrome c-based method useful for the diagnosis and monitoring of fulminant hepatitis.

Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy.

Abstract: Over the past 40 years, hyperbaric oxygen (HBO2) therapy has been recommended and used in a wide variety of medical conditions. In the 1950s, HBO2 was first used as a treatment, in addition to radiation, for head and neck cancers and cervical cancer. Many studies have been conducted to investigate possible therapeutic effects HBO2 as part of cancer management. Evidences showed that HBO2 improved tumor oxygenation, and treatment with HBO2 during irradiation has been shown to improve the radiation response of many solid tumors. It was used for delayed radiation injuries for soft tissue and bony injuries, for symptomatic radiation reactions of the urinary bladder and the bowel, for laryngeal radionecrosis, for radiation-induced optic neuropathy, for radiation-induced proctitis and for radiation-induced necrosis of the brain. HBO2 also increases sensitivity to chemotherapy. A significant improvement in tumor response was obtained when photodynamic therapy (PDT) was delivered during hyperoxygenation. These studies were extensively reviewed and rational scientific basis for further investigations was discussed. The possibility of combining HBO2, PDT and photosensitizers to overcome primary and secondary carcinoma deserve extensive laboratory and clinical research works. HBO2 is a relatively benign with few contraindications, even for active cancer patients.

Creating a peaceful school learning environment: the impact of an antibullying program on educational attainment in elementary schools

Abstract: The impact of a bullying and violence prevention program on education attainment was studied in five elementary schools (K-5), over a 5-year period.A multiple baseline design was used and academic attainment test scores of 1,106 students were monitored before and after the introduction of the program across the school district. This sample was contrasted with an equivalent control sample of 1, 100 students from the school district who attended schools that did not join the program.Program participation was associated with pronounced improvements in the students' achievement test scores. Notable reductions in the scores of those students who left schools with active programs were also observed.This simple, low-cost anti-violence intervention, involves all those who work in schools, not just students. It appears to significantly benefit educational performance of children in the participating elementary schools. The program focuses attention on the interaction between the bully, victim and audience of bystanders who are seen as pivotal in either promoting or ameliorating violence.Buy in to the philosophy by teachers & administration is high, because the format allows each school to create materials with its own personal stamp, and since there is no classroom curriculum add on, the burden to teachers is vastly reduced. Psychiatrists who work with schools could easily assist a school to put the program in place as part of their consultation work.

Early cerebral monitoring using the transcranial Doppler pulsatility index in patients with severe brain trauma.

Abstract: Background: The early posttraumatic period is critical in patients with traumatic brain injury (TBI) because of the increased risk of secondary ischemic injuries to the injured brain. For these patients, cerebral perfusion pressure (CPP) monitoring is recommended. This, however, requires an invasive device to measure intracranial pressure (ICP). Transcranial Doppler (TCD) ultrasoitography is an effective. noninvasive method for the detection of cerebral hemodynamic changes. Use of the dimensionless TCD-pulsatility index (PI) has the advantage of eliminating errors in measurements due to insonation angle variations. Material/Methods: We investigated 37 patients with severe TBI (GCS ≤8 on admission). The TCD parameters included the systolic, diastolic, and mean velocities of the middle cerebral artery (MCV) and the pulsatility index (PI). Mean arterial pressure (MAP), ICP, CPP, and simultaneous arterial and venous blood gases were also measured. Results: We observed a strong correlation between ICP and PI (r=0.82, p 20 mmHG. The con elation of CPP to PI were also statistically significant (P<0.0001 ).The strongest inverse correlation between CPP and PI was obtained (r=0.86, p<0.0001) for CPP values below 70 mmHg. Conclusions: Pulsatility index measurements permit the early identification of patients with low CPP and high risk of cerebral ischemia. In emergency situations it can be used alone when ICP monitoring is contraindicatcd or nor readily available.

Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): The role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress.

Abstract: Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestine and brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin and is stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidase IV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone. Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomical status of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulin release and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacement in diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesis of type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to some extent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers as an anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basal and stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanisms may participate in the pathogenesis of the most common metabolic and behavioral disorders.

Adult neurogenesis in the mammalian central nervous system: functionality andpotential clinical interest.

Abstract: In the past decades, much evidence has confirmed that neurogenesis occurs in the adult brain and that neural stem cells reside in the adult central nervous system, overturning the long-held dogma that we are born with a certain number of nerve cells and that the brain cannot generate new neurons and renew itself. In the adult brain, neurogenesis occurs mainly in two areas: the hippocampus and the subventricular zone, and self-renewing, multipotent neural stem cells have been isolated and characterized in vitro from various regions of the adult central nervous system. Though significant advances have been made in this field of research, the identification and function of neural stem cells in the adult central nervous system remain the source of debate and controversy. Neurogenesis is modulated by several normal and pathologic conditions, suggesting the involvement of the hippocampus and the subventricular zone in a broad range of functions, and that environmental stimuli and pathological conditions may have long-term consequences on the architecture and functioning of the central nervous system. Neurogenesis is involved in processes such as learning, memory, and depression, and may also be involved in regenerative attempts after injuries to the central nervous system. However, the contribution of neurogenesis to these phenomena remains to be elucidated. Neural stem cells also hold the promise to cure a broad range of neurological diseases and injuries. Cell therapeutic interventions may involve both cell transplantation and the stimulation of endogenous neural progenitor cells.

The effect of socioeconomic factors on incidence, stage at diagnosis and survival of cutaneous melanoma.

Abstract: Melanoma represents a significant and growing public health burden worldwide, especially in Caucasian populations. The purpose of this review is to summarize the literature on the relationship between socioeconomic status (SES) and incidence, stage at diagnosis and survival from melanoma. Although differences across countries exist on the relationship of SES to specific behaviors or risk factors, our principal findings are: melanoma is more common in high SES than in low SES populations; and low SES populations present with later stages at diagnosis and experience worse survival rates from melanoma than high SES populations. Potential explanations for these findings are that high SES individuals may have a higher susceptibility and exposure (e.g., risk behaviors) for developing melanoma, and low SES individuals may have less access to educational campaigns and screening examinations and effective treatment. These differences reflect a disparity in melanoma outcomes across diverse SES populations in many countries.

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

Abstract: Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats.

Abstract: BACKGROUND Recently we investigated some neuropharmacological aspects of thymoquinone, such as anticonvulsant, muscle relaxant, and hypnotic effects, as well as its effect on motor coordination and locomotor activity. In this study, we evaluated the effect and mechanism(s) of the action of thymoquinone more precisely via intracerebroventricular (i.c.v.) injection. MATERIAL/METHODS The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using the pentylenetetrazole (PTZ)-induced seizure model. The animals were placed individually in plastic boxes and observed immediately after PTZ injection for a period of 30 min. The latency to and the duration of tonic-clonic seizures were recorded, as well as the percentages of protection against the incidence of seizure and mortality. RESULTS In PTZ-induced epileptic seizures, the i.c.v. injection of thymoquinone at doses of 200 and 400 microM prolonged the time until onset and reduced the duration of tonic-clonic seizures. The protective effect of thymoquinone against lethality was 45% and 50% in the respective doses. In this study, flumazenil (1 nM, i.c.v.) reversed the anticonvulsant activity of thymoquinone. Also, pretreatment with naloxone (10 microM, i.c.v.) antagonized the prolongation of tonic-clonic seizure latency as well as the reduction in seizure duration induced by thymoquinone (200 microM, i.c.v.). CONCLUSIONS These results indicate that thymoquinone may have anticonvulsant activity, probably through an opioid receptor-mediated increase in GABAergic tone.

The efficacy and benefits of environmental control systems for the severely disabled.

Abstract: Background People living with a severe disability suffer substantial personal and social consequences that reduce quality of life (QOL). One potential negative impact on the QOL of a disabled person is the loss of the ability to control devices in their immediate environment (such as the television, computer, telephones, lights, doors, etc.). Consequently, research and development has been conducted on technology designed to restore independence by providing some means of control over these devices. Technology that allows a severely disabled person to gain this type of control has been called an environmental control system (ECS). The aim of this review was to evaluate critically the status and efficacy of ECS technology for the severely disabled. Materials/methods To achieve this, a comprehensive database search was conducted for relevant material on technical and clinical aspects of ECS control. Results The review demonstrated that there is an abundance of work conducted on ECS technology, resulting in a number of creative control systems that are designed to be used by the severely disabled. These include switching systems that utilize voice, muscle, brain activity, head motion, eye blink, breath, chin, and so on. However, the review also established that rarely has the efficacy of these systems been scientifically established. Conclusions Severely disabled persons need access to ECS technology that has been shown to be efficacious. While the severely disabled gain benefits from using ECS technology, challenges still exist before ECS technology for the severely disabled can provide highly reliable and user-friendly device control.

Correlation between acoustic speech characteristics and non-speech motor performance in Parkinson Disease

Abstract: Background Research has found that non-speech motor deficits in Parkinson Disease (PD) can be consistently improved by levodopa medications and surgical treatment, but that speech and voice are only partially responsive to treatment. This has led to the assertion that speech is an axial (non-peripheral) feature of PD, along with other features that are only partially responsive to treatment (e.g., postural stability and gait). The current study tested this assertion via examination of the relationship between multiple measures of speech production and multiple measures of non-speech movement in individuals with PD. Material/methods Nine individuals with idiopathic PD were studied, and all participants were taking levodopa-carbidopa medication. Motor performance was examined using the motor portion of the Unified Parkinson's Disease Rating Scale, and speech was examined via acoustic analysis of phonation, articulation, and prosody. Results Seven of sixteen speech acoustic measures (FoSD in vowels, F2 slope for /u/ and /ae/, FoSD in reading, articulation rate in monologue, and percent pause in reading and monologue) were significantly correlated with non-speech movements. Results suggested that speech measures are correlated with both axial motor symptoms (e.g., gait, facial expression, posture, postural stability) and non-axial motor symptoms (e.g., rest tremor, left and right bradykinesia, postural tremor). Conclusions It has been hypothesized that axial symptoms of PD are more purely dopaminergic, and non-axial symptoms are related to non-dopaminergic lesions. Therefore, the current results indicate that certain speech deficits in PD may result from dopaminergic lesions, while others appear to result from non-dopaminergic lesions.

Epidemiology of the diabetic foot in Africa

Abstract: Diabetes mellitus is the most common, non-communicable chronic disease globally. In African countries, peripheral neuropathy underlies most diabetic foot complications; however, peripheral vascular disease appears to be increasing, presumably a reflection of increasing urbanisation. We conducted this study to ascertain the occurrence of foot complications among diabetes patients in the African continent. Using various keyword combinations, we searched Medline (PubMed) databases and the archives of Muhimbili National Hospital, the major teaching hospital in Tanzania, for obscure diabetes literature on diabetes in Africa. We also reviewed available non-English literature and obtained relevant translations where appropriate. We found articles encompassing years 1960-2003. Foot complications such as ulceration, infection, or gangrene were generally associated with considerable long-term disability and pre-mature mortality. Rates of complications varied by country-foot ulcers: 4-19%; peripheral neuropathy: 4-84.4%; peripheral vascular disease: 2.9-78.7%; frequency of patients presenting with gangrenous foot ulcers: 0.6-69%; foot amputation rates: 0.3-45%. A study of diabetic patients in Tanzania showed mortality rates >50% among patients with severe foot ulcers, who did not undergo surgery. Other published data from Tanzania suggest that surgical intervention after the onset of gangrene may be too late to prevent death. Prevention and control programmes are needed to stem the rising occurrence of diabetic foot complications in Africa. Gangrenous diabetic feet require aggressive management and early surgical intervention. Early presentation by patients and prompt surgical intervention during less severe rather than during later stages of an ulcer may improve patients outcome and reduce mortality rates.

Mechanisms of MPTP toxicity and their implications for therapy of Parkinson's disease.

Abstract: Parkinson's disease is one of the major neurodegenerative disorders. This disease is mainly characterized by tremor, bradykinesia, rigidity and postural instability that results primarily from a loss of dopaminergic neurons of nigrostriatal pathway. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is well known to damage the nigrostriatal dopaminergic pathway as seen in Parkinson's disease. Recent evidence shows that glial-related response plays a key role in the MPTP neurotoxic process and the blockade of glial activation may be a new therapeutic approach, which has applicability for Parkinson's disease. On the other hand, dopamine transporters (DAT) are important to the appearance of MPTP neurotoxicity because to be neurotoxin, an MPTP metabolite must first gain access to the dopaminergic neurons via DAT. Several studies suggest that DAT is a mandatory factor for expression of MPTP neurotoxicity and may explain the selective neuronal damage in the substantia nigra in MPTP toxicity. Therefore, DAT is thought to play an important role in the MPTP neurotoxic process and specific blockade of DAT with high-affinity inhibitors in neurodegenerative diseases such as Parkinson's disease, where the effective levels of dopamine are markedly reduced, may have beneficial consequences. In view of these new insights, this article suggests that the overexpression of S100beta protein secreted by glial cells may be an exacerbating factor in the neurodegeneration of dopaminergic cells. In this review, we also demonstrate the possible role of DAT in the brain cells in MPTP neurotoxicity. Thus this review provides valuable information for progressive neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.

A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis.

Abstract: Summary Background: Thimerosal is an ethylmercury-containing preservative in vaccines. Toxicokinetic studies have shown children received doses of mercury from thimerosal-containing vaccines (TCVs) that were in excess of safety guidelines. Previously, an ecological study showing a signifi cant association between TCVs and neurodevelopmental disorders (NDs) in the US was published in this journal. Material/Methods: A two phased population-based epidemiological study was undertaken. Phase one evaluated reported NDs to the Vaccine Adverse Event Reporting System (VAERS) following thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccines in comparison to thimerosal-free DTaP vaccines administered from 1997 through 2001. Phase two evaluated the automated Vaccine Safety Datalink (VSD) for cumulative exposures to mercury from TCVs at 1-, 2-, 3-, and 6-monthsof-age for infants born from 1992 through 1997 and the eventual risk of developing NDs. Results: Phase one showed signifi cantly increased risks for autism, speech disorders, mental retardation, personality disorders, and thinking abnormalities reported to VAERS following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. Phase two showed signifi cant associations between cumulative exposures to thimerosal and the following types of NDs: unspecifi ed developmental delay, tics, attention defi cit disorder (ADD), language delay, speech delay, and neurodevelopmental delays in general. Conclusions: This study showed that exposure to mercury from TCVs administered in the US was a consistent signifi cant risk factor for the development of NDs. It is clear from these data and other recent publications linking TCVs with NDs that additional ND research should be undertaken in the context of evaluating mercury-associated exposures and thimerosal-free vaccines should be made available.

Semicarbazide-sensitive amine oxidase (SSAO): from cell to circulation.

Abstract: Semicarbazide-sensitive amine oxidase (SSAO) is a multi-functional enzyme widely present in nature. It converts primary amines into their corresponding aldehydes, while generating H(2)O(2) and NH(3). In mammals, SSAO circulates in plasma, while a membrane-bound form (often referred to as vascular adhesion protein-1, VAP-1) is found in many tissues and organs, especially in adipocytes and vascular endothelial and smooth muscle cells. In recent years, evidence has been accumulating that SSAO has a role in protein cross-linking, formation of advanced glycation end-products, atherogenesis, glucose regulation and leukocyte extravasation at inflammation sites. Plasma SSAO is quite stable in healthy adults, but is elevated in diabetes mellitus (both type 1 and type 2), congestive heart failure and liver cirrhosis. The origin of circulating SSAO remains unclear, but recent evidence from clinical studies and from (transgenic) animal studies suggests that adipocytes and vascular endothelial cells may be the most important source. Studies with cell cultures show evidence that the membrane-bound SSAO can be split off from the cells, thus giving rise to the (truncated) circulating form of SSAO. In some pathological conditions the diseased organ may be the main source of the elevated plasma SSAO. Little is known as yet about the regulation of plasma SSAO. Thyroid hormone appears to play a (modest) role in this respect. Further evidence from clinical, animal and cell-culture studies, helped by the new availability of selective SSAO inhibitors, is needed to shed more light on the question of the regulation of SSAO.

Ceruloplasmin - acute-phase reactant or endogenous antioxidant? The case of cardiovascular disease.

Abstract: Ceruloplasmin is a plasma protein that functions as a copper transporter. Epidemiological studies have indicated an association between the concentration of this protein and risk for cardiovascular disease. The mechanism for the involvement of ceruloplasmin in cardiovascular disease and other conditions is not yet clear, although it is widely accepted that the role played by ceruloplasmin in facilitating or counteracting oxidative stress is central. We review here some of the studies on this issue and try to calm down the duel between the claims supporting the oxidant or the antioxidant effects of ceruloplasmin through a clear-cut analysis of the available data. Our conclusion is that a verdict regarding the pathogenetic involvement of ceruloplasmin in cardiovascular disease should await further research.

Association between oxygen consumption and nitric oxide production during the relaxation response.

Abstract: Background Mind/body practices that elicit the relaxation response (RR) are currently practiced by over 30% of American adults. RR elicitation reduces volumetric oxygen consumption (VO(2)) from rest and counteracts the effects of stress, although the mechanisms mediating the RR remain unknown. This study was designed to investigate whether RR elicitation is mediated by nitric oxide (NO). We developed a method to quantify depth of RR using change in VO(2) (slope) during RR elicitation. We evaluated whether depth of RR elicitation was correlated with changes in NO, as measured by percentage changes in fractional exhaled nitric oxide (F(E)NO). Material/methods We conducted a randomized, controlled trial, in which 46 subjects were randomized to either 8-weeks of RR training using audiotapes (n=34) or 8-weeks of exposure to a control condition--receiving health-education by audiotapes (n=12). Prior to randomization, VO(2) and F(E)NO were measured while subjects listened to a control audiotape. Eight weeks later, VO(2) and F(E)NO were measured while the RR group listened to a RR-eliciting audiotape and the control group listened to a control audiotape. Results Prior to receiving any training, there was no association between VO(2) slope and F(E)NO. After training, there was an inverse correlation between VO(2) slope and F(E)NO in the RR group (r = -0.41, P=0.037, n=26), but not in the control group (r=0.12, P=0.78, n=8). Conclusions Depth of RR elicitation was associated with increased concentrations of F(E)NO after RR training. The RR may be mediated by NO helping to explain its clinical effects in stress-related disorders.