The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jpi.12267

Melatonin: an ancient molecule that makes oxygen metabolically tolerable.

Trease and Evans' pharmacognosy

Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.

Prospective Analysis of the Insulin-Resistance Syndrome (Syndrome X)

Background and Objectives: Antimicrobial photodynamic therapy (APDT) employs a non-toxic photosensitizer (PS) and visible light, which in the presence of oxygen produce reactive oxygen species (ROS), such as singlet oxygen (^(1)O_2, produced via Type II mechanism) and hydroxyl radical (HO., produced via Type I mechanism). This study examined the relative contributions of ^(1)O_2 and HO. to APDT killing of Gram-positive and Gram-negative bacteria.
Study Design/Materials and Methods: Fluorescence probes, 3′-(p-hydroxyphenyl)-fluorescein (HPF) and singlet oxygen sensor green reagent (SOSG) were used to determine HO. and ^(1)O_2 produced by illumination of two PS: tris-cationic-buckminsterfullerene (BB6) and a conjugate between polyethylenimine and chlorin(e6) (PEI–ce6). Dimethylthiourea is a HO. scavenger, while sodium azide (NaN_3) is a quencher of ^(1)O_2. Both APDT and killing by Fenton reaction (chemical generation of HO.) were carried out on Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa).
Results: Conjugate PEI-ce6 mainly produced ^(1)O_2 (quenched by NaN_3), while BB6 produced HO. in addition to ^(1)O_2 when NaN_3 potentiated probe activation. NaN_3 also potentiated HPF activation by Fenton reagent. All bacteria were killed by Fenton reagent but Gram-positive bacteria needed a higher concentration than Gram-negatives. NaN3 potentiated Fenton-mediated killing of all bacteria. The ratio of APDT killing between Gram-positive and Gram-negative bacteria was 2 or 4:1 for BB6 and 25:1 for conjugate PEI-ce6. There was a NaN_3 dose-dependent inhibition of APDT killing using both PEI-ce6 and BB6 against Gram-negative bacteria while NaN_3 almost failed to inhibit killing of Gram-positive bacteria.
Conclusion: Azidyl radicals may be formed from NaN_3 and HO.. It may be that Gram-negative bacteria are more susceptible to HO. while Gram-positive bacteria are more susceptible to ^(1)O_2. The differences in NaN_3 inhibition may reflect differences in the extent of PS binding to bacteria (microenvironment) or differences in penetration of NaN_3 into cell walls of bacteria.

Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on Gram-negative and Gram-positive bacteria

The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates in Palestine. Association between self-reported sleep quality and self-reported academic achievement was also investigated. Sleep habits and problems were investigated using a convenience sample of students from An-Najah National University, Palestine. The study was carried out during spring semester, 2009. A self-administered questionnaire developed based on The Diagnostic and Statistical Manual of Mental Disorders IV criteria and Pittsburgh Sleep Quality Index was used. 400 students with a mean age of 20.2 ± 1.3 were studied. Reported mean duration of night sleep in the study sample was 6.4 ± 1.1 hours. The majority (58.3%) of students went to bed before midnight and 18% of the total sample woke up before 6 am. Sleep latency of more than one hour was present in 19.3% of the students. Two thirds (64.8%) of the students reported having at least one nocturnal awakening per night. Nightmares were the most common parasomnia reported by students. Daytime naps were common and reported in 74.5% of the study sample. Sleep quality was reported as "poor" in only 9.8% and was significantly associated with sleep latency, frequency of nocturnal awakenings, time of going to bed, nightmares but not with academic achievement. Sleep habits among Palestinian undergraduates were comparable to those reported in European studies. Sleep problems were common and there was no significant association between sleep quality and academic achievement.

/pdf/sleep-habits-and-sleep-problems-among-palestinian-students-3fdxjz95gc.pdf

Sleep habits and sleep problems among Palestinian students

We investigated the ability of reactive oxygen species (ROS), such as hydrogen peroxide (H(2)O(2)), hydroxyl radical ((·)OH), and hypochlorous acid (HOCl), to overcome the defensive capacity of cumulus cells and elucidate the mechanism through which ROS differentially deteriorate oocyte quality. Metaphase II mouse oocytes with (n = 1634) and without cumulus cells (n = 1633) were treated with increasing concentration of ROS, and the deterioration in oocyte quality was assessed by the changes in the microtubule morphology and chromosomal alignment. Oocyte and cumulus cell viability and cumulus cell number were assessed by indirect immunofluorescence, staining of gap junction protein, and trypan blue staining. The treated oocytes showed decreased quality as a function of increasing concentrations of ROS when compared to controls. Cumulus cells show protection against H(2)O(2) and (·)OH insult at lower concentrations, but this protection was lost at higher concentrations (>50 μmol/L). At higher H(2)O(2) concentrations, treatment dramatically influenced the cumulus cell number and viability with resulting reduction in the antioxidant capacity making the oocyte more susceptible to oxidative damage. However, cumulus cells offered no significant protection against HOCl at any concentration used. In all circumstances in which cumulus cells did not offer protection to the oocyte, both cumulus cell number and viability were decreased. Therefore, the deterioration in oocyte quality may be caused by one or more of the following: a decrease in the antioxidant machinery by the loss of cumulus cells, the lack of scavengers for specific ROS, and/or the ability of the ROS to overcome these defenses.

The Defensive Role of Cumulus Cells Against Reactive Oxygen Species Insult in Metaphase II Mouse Oocytes.

Metabolic syndrome (MS) is a cluster of the most dangerous cardiac risk factors and is associated with high mortality. Ethnic differences in metabolic syndrome (MS) criteria and prevalence rates have been reported. The purpose of this study was to investigate the MS prevalence among patients with schizophrenia in Palestine. We recruited 250 patients with schizophrenia from 4 psychiatric primary healthcare centers in Northern Palestine. The MS prevalence was assessed based on National Cholesterol Education Program Adult Treatment Panel III Adapted criteria. The overall MS prevalence was 43.6%, with 39% in male and 55.9% in female patients. On average, the study patients had 2.3 ± 1.3 metabolic abnormalities. Univariate analysis showed that MS was significantly higher with older age, female gender, longer duration of the illness, smoking, abdominal obesity, high systolic and diastolic blood pressure, high triglycerides, low HDL-C, and high fasting plasma glucose. Multiple logistic regression analysis showed that only systolic blood pressure, high triglycerides, high fasting plasma glucose, and low HDL-C were significant predictors of MS in schizophrenic patients. MS is common among Arab patients with schizophrenia. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.

/pdf/prevalence-of-metabolic-syndrome-among-patients-with-3aq6i11bw6.pdf

Prevalence of metabolic syndrome among patients with Schizophrenia in Palestine

Throughout history, every civilization in the world used plants or their derivatives for treatment or prevention of diseases. In Palestine as in many other countries, herbal medicines are broadly used in the treatment of wide range of diseases including urological diseases. The main objective of this research is to study the use of herbal remedies by herbalists and traditional healers for treatment of various urological diseases in the West Bank regions of Palestine and to assess their efficacy and safety through the literature review of the most cited plants. The study included a survey part, plant identification and a review study. The first part was a cross-sectional descriptive study. Face to face questionnaires were distributed to 150 traditional healers and herbalist in all regions of the West Bank of Palestine. The literature review part was to assess the most cited plants for their efficacy and toxicity. One hundred forty four herbalists and traditional healers accepted to participate in this study which was conducted between March and April, 2016. The results showed that 57 plant species belonging to 30 families were used by herbalists and traditional healers for treatment of various urinary tract diseases in Palestine. Of these, Apiaceae family was the most prevalent. Paronychia argentea, Plantago ovata, Punica granatum, Taraxacum syriacum, Morus alba and Foeniculum vulgare were the most commonly used plant species in the treatment of kidney stones, while Capsella bursa-pastoris, Ammi visnaga and Ammi majus were the most recommended species for treatment of urinary tract infections and Portulaca oleracea used for renal failure. In addition Curcuma longa and Crocus sativus were used for enuresis while Juglans regia, Quercus infectoria, Sambucus ebulus and Zea mays were used for treatment symptoms of benign prostate hyperplasia. Fruits were the most common parts used, and a decoction was the most commonly used method of preparation. Through literature review, it was found that Paronychia argentea has a low hemolytic effect and contains oxalic acid and nitrate. Therefore, it could be harmful to renal failure patients, also Juglans regia, Quercus infectoria and, Sambucus ebulus are harmful plants and cannot be used for treatment of any disease. Our data provided that ethnopharmacological flora in the West Bank regions of Palestine can be quite wealthy and diverse in the treatments of urinary tract diseases. Clinical trials and pharmacological tests are required evaluate safety and efficacy of these herbal remedies.

/pdf/ethnopharmacological-survey-of-medicinal-plants-practiced-by-486p2p6w41.pdf

Ethnopharmacological survey of medicinal plants practiced by traditional healers and herbalists for treatment of some urological diseases in the West Bank/Palestine.

Iyad Ali

Papers

Sleep habits and sleep problems among Palestinian students

The Defensive Role of Cumulus Cells Against Reactive Oxygen Species Insult in Metaphase II Mouse Oocytes.

Prevalence of metabolic syndrome among patients with Schizophrenia in Palestine

Ethnopharmacological survey of medicinal plants practiced by traditional healers and herbalists for treatment of some urological diseases in the West Bank/Palestine.

Hemolysis of human red blood cells by combination of riboflavin and aminophylline.