I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

Ghrelin, a novel GH-releasing peptide isolated from human and rat stomach, stimulates food intake and GH secretion. We determined plasma ghrelin concentrations in patients with simple obesity, anorexia nervosa, and type 2 diabetes mellitus by RIA. We also studied plasma ghrelin responses to glucose load and meal intake and obtained a 24-h profile of circulating ghrelin in humans. Plasma ghrelin concentrations in patients with simple obesity and anorexia nervosa were lower and higher, respectively, than those of healthy subjects with normal body weight. Among those with type 2 diabetes mellitus, obese patients had lower and lean patients higher fasting plasma ghrelin concentrations than normal-weight patients. Fasting plasma ghrelin concentration was negatively correlated with body mass index in both nondiabetic and diabetic patients. Plasma ghrelin concentrations of normal subjects decreased significantly after oral and iv glucose administration; a similar response was also observed in diabetic patients a...

Plasma Ghrelin Levels in Lean and Obese Humans and the Effect of Glucose on Ghrelin Secretion

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)
are associated with skeletal muscle complaints, including clinically important
myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia
with and without elevated CK levels, muscle weakness, muscle cramps, and persistent
myalgia and CK elevations after statin withdrawal. We performed a literature
review to provide a clinical summary of statin-associated myopathy and discuss
possible mediating mechanisms. We also update the US Food and Drug Administration
(FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy
were identified via a PubMed search through November 2002 and articles on
statin clinical trials, case series, and review articles were identified via
a PubMed search through January 2003. Adverse event reports of statin-associated
rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature
review found that reports of muscle problems during statin clinical trials
are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of
statin-associated rhabdomyolysis reported between January 1, 1990, and March
31, 2002. Cerivastatin was the most commonly implicated statin. Few data are
available regarding the frequency of less-serious events such as muscle pain
and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis
and other adverse effects with statin use can be exacerbated by several factors,
including compromised hepatic and renal function, hypothyroidism, diabetes,
and concomitant medications. Medications such as the fibrate gemfibrozil alter
statin metabolism and increase statin plasma concentration. How statins injure
skeletal muscle is not clear, although recent evidence suggests that statins
reduce the production of small regulatory proteins that are important for
myocyte maintenance.

https://jamanetwork.com/journals/jama/articlepdf/196305/JSC20298.pdf

Statin-Associated Myopathy

Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. Defenses against free radical damage include tocopherol (vitamin E), ascorbic acid (vitamin C), beta-carotene, glutathione, uric acid, bilirubin, and several metalloenzymes including glutathione peroxidase (selenium), catalase (iron), and superoxide dismutase (copper, zinc, manganese) and proteins such as ceruloplasmin (copper). The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.

Free radical tissue damage: protective role of antioxidant nutrients.

https://escholarship.org/content/qt6nx7k5zw/qt6nx7k5zw.pdf?t=qlup1r

Lipidomics reveals a remarkable diversity of lipids in human plasma

Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.

Evidence of Plasma CoQ10‐Lowering Effect by HMG‐CoA Reductase Inhibitors: A Double‐Blind, Placebo‐Controlled Study

Coenzyme Q10 in essential hypertension

Coenzyme Q10 (CoQ10) levels were assayed in total seminal fluid or both in seminal fluid and seminal plasma in 77 subjects with normal or pathological findings at standard semen analysis CoQ10 levels showed a significant correlation with sperm count and with sperm motility An interesting exception was constituted by patients with varicocele, in whom the correlation with sperm concentration was preserved, whereas the correlation with sperm motility was lacking Moreover, they showed an increased ratio of plasma CoQ to total seminal CoQ10 in comparison with the other subjects These data suggest a pathophysiological meaning of CoQ10 in human seminal fluid and a possible molecular defect in varicocele patients CoQ10 measurement could represent an important examination in infertile patients; moreover, from these results a rationale might arise for a possible treatment with exogenous CoQ10 in dyspermic patients

Coenzyme Q10 concentrations in normal and pathological human seminal fluid.

Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(l–44) (50 μg, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 ± 5.6 (±se) μg/L in normal women, 8.2 ± 1.3 μg/L in obese women, and 53.2 ± 7.7 μg/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was −64.2% in normal women, −64.9% in obese women, and −55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (−60.9%) and 1300 h (−34.6%) compared with the fasting peak responses. In ...

Differential Effects of Feeding on the Ultradian Variation of the Growth Hormone (GH) Response to GHReleasing Hormone in Normal Subjects and Patients With Obesity and Anorexia Nervosa

Neutrophil chemiluminescence was determined in patients with active rheumatoid arthritis. Twelve patients were randomly assigned either to a diet high in polyunsaturated fatty acids supplemented with eicosapentaenoic and docosahexaenoic acids or to a diet high in saturated fatty acids. A correlation with clinical and laboratory parameters is also reported. No statistical difference was observed in neutrophil chemiluminescence and in clinical parameters in the group of patients treated with a diet high in saturated fatty acids. Fish oil ingestion resulted in subjective alleviation of active rheumatoid arthritis and reduction of neutrophil chemiluminescence. This study corroborates the hypothesis of an anti-inflammatory role for polyunsaturated fatty acids in patients with chronic inflammatory diseases.

https://ard.bmj.com/content/annrheumdis/47/10/793.full.pdf

Alessandro Oradei

Papers

Evidence of Plasma CoQ10‐Lowering Effect by HMG‐CoA Reductase Inhibitors: A Double‐Blind, Placebo‐Controlled Study

Coenzyme Q10 in essential hypertension

Coenzyme Q10 concentrations in normal and pathological human seminal fluid.

Differential Effects of Feeding on the Ultradian Variation of the Growth Hormone (GH) Response to GHReleasing Hormone in Normal Subjects and Patients With Obesity and Anorexia Nervosa

Influence of diet with different lipid composition on neutrophil chemiluminescence and disease activity in patients with rheumatoid arthritis.