Daily apple versus dried plum: impact on cardiovascular disease risk factors in postmenopausal women

BackgroundEvidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings.ObjectiveWomen experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women.DesignOne-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained.ResultsNeither of the dried fruit regimens significantly affected the participants' reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months.ConclusionsThere were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties.     

Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect.

Metformin, a commonly used antidiabetic drug, exerts its glucose-lowering effect due to metabolic activities at several sites of action (biophases), including liver, intestine, muscle cells, and adipocytes. The relative contribution of the individual biophases to the overall glucose-lowering effect is not known. Thus, the aims of this investigation were to study the influence of mode of drug administration on the kinetics of glucose-lowering action of metformin in diabetic rats and identify the contribution of different sites of action to the overall response. Streptozotocin diabetic rats received metformin in crossover fashion via intraduodenal, intravenous, and intraportal routes as bolus dose or infusion regimens designed to yield similar pharmacokinetic profiles. Metformin plasma concentrations and blood glucose levels were measured following each mode of administration. Despite the similarity in the concentration-time profiles obtained for different routes of metformin administration, intraduodenal administration produced larger response than intraportal metformin infusion, and lowest response was observed following intravenous administration. This finding indicates that a significant "first-pass" pharmacodynamic effect, which occurs in the presystemic sites of action (liver and the gastrointestinal wall), contributes to the overall glucose-lowering response of metformin. We applied a combined pharmacokinetic-pharmacodynamic modeling approach to study the nature of the first-pass pharmacodynamic effect. The observed data were successfully described by a novel integrated indirect response pharmacokinetic-pharmacodynamic model that revealed a correlation between the temporal metformin concentrations that transit the portal vein and through the gut wall rather than with drug concentrations that accumulated in the liver and the intestinal wall.     

The association between two common mutations C677T and A1298C in human methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathy in type II diabetic patients

Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephropathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whose association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes mellitus (DM). Both A1298C and C677T are highly prevalent in the diabetic population with allele frequencies of 0.35 and 0.36, respectively. The genotype frequency and allele frequency for these two polymorphisms in patients who are normoalbuminuric (n = 55) were compared with those of patients who had either micro- or macroalbuminuria (n = 43). For both polymorphisms, there were no significant differences in either the genotype distribution or allele frequency in patients with or without DN. However, in patients with serum folate <15.4 nmol/L, there was a greater incidence of DN in those patients who were homozygous or heterozygous for the C677T mutation. For the A1298C mutation, there is evidence suggesting that the homozygous state may be protective in patients with low-normal serum folate. Folate supplementation in diabetic patients with the C677T mutation and low-normal serum folate may prevent the onset or retard the progression of DN.     

Identification of glycogen synthase kinase-3 inhibitors with a selective sting for glycogen synthase kinase-3α

The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-3α and GSK-3β to AD pathology and AML is ongoing. Thus, the identification of potent GSK-3α-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-3α inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-3α selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.     

The effect of contrast and luminance on mfERG responses in a monkey model of glaucoma

PURPOSE: To evaluate the effect of contrast and luminance attenuation on the multifocal electroretinogram (mfERG) responses of normal and glaucomatous eyes of cynomolgus monkeys. METHODS: Nine adult male cynomolgus monkeys with unilateral experimentally induced glaucoma were used. Hypertension-induced damage was confirmed by tomography of the optic disc. mfERGs were recorded with five different stimulus contrasts and/or luminance settings. The first-order and the first slice of second-order responses were analyzed. RESULTS: Waveforms of normal and glaucomatous eyes differed in shape and amplitude. Second-order responses contributed to first-order responses of the signals in the normal eyes, but made a negligible contribution to the signals in the glaucomatous eyes. Contrast and luminance attenuation affected both first- and second-order responses. The differences between signals in normal and glaucomatous eyes were sufficiently large for an unsupervised clustering algorithm to achieve accurate segregation. CONCLUSIONS: The observations in this study indicate that outer and inner retinal generators participate in first-order mfERG responses and that both inner and outer retinal contributors respond to contrast and luminance changes in stimulus. The hypertension-induced changes in the mfERG furthermore suggest damage to both inner and outer retina.     

Diagnostic tests for geriatric incontinence

Summary A series of simplified diagnostic tests were used in conjunction with a clinical algorithm by a nurse practitioner to assess and plan management for 50 incontinent geriatric females. The simplified tests had a positive predictive value of 91%, a sensitivity of 91% and a specificity of 80% for detrusor motor instability or hyperreflexia, diagnosed in 70% of these patients by a standard water filling multichannel cystometrogram performed by an experienced urologist. Based on the results of the simplified tests and a straightforward clinical algorithm, the nurse practitioner was able to develop an appropriate management plan for 44 (88%) of the patients. The simplified diagnostic tests, which can be performed in a clinic or at the patient's bedside in a nursing home or hospital, should help primary care health professionals to diagnose one of the most common and treatable causes of incontinence in the elderly, and to identify patients who might benefit from further urologic, gynecologic or urodynamic evaluation.Data presented in this paper were presented at the annual meetings of the International Continence Society (London, September, 1985) and the Gerontological Society of America (New Orleans, November, 1985)Supported by NIH Grant No. AG04586, grants from the Robert Woods Johnson Foundation and the Max Factor Family Foundation, and by an Academic Award for the National Institute on Aging (AG00189; Dr. Ouslander)     

Congenital short-bowel and malrotation: clinical presentation and outcome of six affected offspring in three related families.

Newborns with congenital short small bowel associated with malrotation and intestinal dysmotility have a uniformly bad prognosis. However, few long-term survivors have been reported, suggesting that the disorder is not invariably fatal. The majority of cases previously reported were familial. We report on six affected siblings in three related families. The aim of this report is to assess the mode of inheritance, the expression of this disorder, and to point to the correlation between the onset of gastrointestinal symptoms and the outcome.     

Pulmonary manifestations in Beh?et's syndrome

Among 72 patients with Beh?et's syndrome, seven had pulmonary vascular involvement. Additional data from 42 cases in the literature are discussed. Recurrent episodes of dyspnea, cough, chest pain, and hemoptysis were the primary clinical signs, mainly in young men, appearing 3.6 years after the first manifestation of Beh?et's syndrome. Fever, elevated ESR, and anemia were common, and chest x-ray films showed pulmonary infiltrates, pleural effusions, and prominent pulmonary arteries. Ventilation-perfusion scans showed perfusion defects even when chest x-ray films were normal. Pulmonary artery aneurysms were seen in 7/13 in whom angiography was done. Of 42 patients, 16 died, 15 from fatal pulmonary hemorrhage, 80 percent within two years from the development of pulmonary disease. Histopathologic study results showed vasculitis of pulmonary vessels of various sizes, leading to thrombosis, destruction of the elastic laminae, aneurysms, and arteriobronchial fistula. In addition, pulmonary emboli and the aphthous lesion of the tracheobronchial tree may aid the clinical picture. Anticoagulant therapy may be hazardous in patients with aneurysmal dilatation of the pulmonary vascular tree, and the beneficial effect of corticosteroid therapy is discussed. Pulmonary vasculitis in Beh?et's syndrome is a unique clinical and pathologic picture, differing from other vasculitides affecting the lung, presents a major threat to the patient's life.     

Female urethral obstruction after Marshall-Marchetti-Krantz operation

During the last 5 years 13 neurologically normal women were seen with urodynamically proved urethral obstruction after a Marshall-Marchetti-Krantz operation. These obstructed patients were treated by a simple transvaginal procedure consisting of complete urethrolysis followed by a needle urethrovesical resuspension procedure. Postoperatively, 12 patients experienced complete disappearance of the presenting symptoms, return to a normal voiding pattern and decreased residuals of urine to less than 50 cc. The remaining patient, although urodynamically unobstructed, had to remain on intermittent catheterization. The pathophysiology, diagnosis and treatment of this iatrogenic type of female urethral obstruction are discussed.     

To trim or replant: A matter of cost

Many factors are involved in the decision whether to complete the amputation of an injured digit and trim the stump or to replant the amputated member. This paper compares the cost of these two treatments so that this financial aspect might be included among the many factors which influence the surgeon's decision. The cost of these treatments was separated into two aspects. First, the overall cost of the medical and surgical expenses was calculated. Second, the cost which the Israeli social security granted the injured worker due to the disability was calculated. By comparing the total surgical and medical costs of amputations and replantations, trimming is far less expensive than replantation. In the long run, the compensation the insurer owes the disabled trimmed patient is far higher than the compensation given to those who were successfully replanted, provided the injured worker has a certain number of working years to retirement and has a yearly income of a certain level. Thus, in most cases, replantation is recommended from the cost benefit aspect.

---

Resumen Muchos factores resultan involucrados cuando uno se enfrenta a decidir si debe completar una amputación digital y revisar el muñion, o reimplantar el miembro amputado. El présente artículo se refiere al costo de estas dos modalidades de tratamiento, las cuales compara, con el objeto de definir si el aspecto financiero debe quedar incluido entre los multiples factores que pueden influenciar la decisión del cirujano. El costo de estas dos modalidades de tratamiento fue discriminado en dos aspectos: se calculó el costo global de los gastos médicos y quirúrgicos; luego se calculó el costo que la seguridad social de Israel asigna al trabajador lesionado según la incapacidad. Al comparar los costos totales de las amputaciones y reimplantaciones apareció evidente que la revisión del muñon es mucho menos costoso en cuanto a los gastos médicos y quirúrgicos. Sin embargo, a largo plazo resulta bastante más alta la compensación que el asegurador otorga al paciente que aquella que se otorga a quien haya sido exitosamente reimplantado, siempre y cuando el trabajador tenga por delante un cierto número de años de trabajo hasta su jubilación y su nivel de ingreso sea de cierto nivel. Por ello en la mayoría de los casos se recomienda la reimplantación también por razones de costo beneficio.

---

Résumé Bien des facteurs doivent être pris en considération avant de décider quelle amputation partielle de doigt mérite d'être complétée, quel moignon régularisé, ou quelle amputation complète réimplantée. Cet article traite du coût des types de traitement et les compare afin de déterminer si l'aspect financier pourrait également être un facteur qui influence la décision chirurgicale. Le coût de ces traitements comporte deux aspects. Premièrement, il faut calculer le coût global des dépenses médicales et chirurgicales. Ensuite entre en ligne de compte le coût de la compensation accordée par la Sécurité Sociale basée sur l'incapacité de travail. En comparant ces coûts pour chaque type de lésion, il était évident que la régularisation d'une amputation était bien moins chère qu'une réimplantation. Par contre, à la longue, les pensions versées au blessé régularisé mais handicapé étaient de loin plus coûteuses que le prix d'une réimplantation à condition que l'ouvrier ne soit pas près de la retraite et que son salaire annuel atteigne un certain niveau. Ainsi calculé, il ressort que la réimplantation est recommandée d'un point de vue économique global.