Muscarinic receptor antagonist-induced lenticular opacity in rats.

Investigations on compound A, an M2-sparing M3 muscarinic receptor antagonist, showed that focal polar anterior subcapsular lenticular opacities, characterized by focal epithelial proliferation, developed in Sprague-Dawley rats. The incidence and bilateral localization of this change increased generally with dose and time, though plateauing after 8 months of treatment; however the severity progressed very slightly. Over a 1-year period, no anterior cortical lens fiber changes or other histological ocular changes developed. A decreased severity of the change and apoptosis suggested some regression after a 26-week recovery period. Two nonselective muscarinic receptor antagonists, atropine and tolterodine, induced similar lenticular changes in rats. A hypothesis in relation to an indirect effect of the drug, such as increased illumination of the lens due to mydriasis observed with all these compounds, was investigated and disproven. Because these opacities are induced by structurally unrelated muscarinic receptor antagonists (atropine and tolterodine), it is likely that these lenticular changes are the result of muscarinic receptor inhibition. However, hypotheses regarding a direct effect of the drug on muscarinic receptors in the lens epithelium, possibly mediated by drug and/or metabolite(s) in the aqueous humor and/or lens epithelium, remain to be investigated. This lenticular opacity is similar to that observed spontaneously in Sprague-Dawley rats, although the latter occur at a lower incidence. No such lenticular opacities have been reported in other animal species, including man, after treatment with muscarinic receptor antagonists.     

Prevalence of pelvic floor disorders in women with suspected gynecological malignancy: a survey-based study

Introduction and hypothesis

Understanding of pelvic floor disorders among women with gynecological cancer is limited. The objective of this study was to describe the prevalence of pelvic floor disorders in women with suspected gynecological malignancy before surgery.

Methods

A cross-sectional study was performed of women aged ≥18 with a suspected gynecological malignancy who enrolled in the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC) from August 2012 to June 2013. Demographics were obtained from the HR/CSC self-reported data; clinical data were abstracted from the electronic medical record. Subjects completed validated questionnaires (Rotterdam Symptom Checklist and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms) to assess bladder and bowel function.

Results

Among 186 women scheduled for surgery for gynecological malignancy, 152 (82 %) completed baseline assessments before surgery. Mean age was 58.1?±?13.3 years, and mean BMI was 33.6?±?8.8 kg/m². The majority of subjects had uterine cancer (61.8 %), followed by ovarian (17.1 %) and cervical (11.1 %). At baseline, the rate of urinary incontinence (UI) was 40.9 %. A third of subjects reported stress UI, and one quarter reported urge UI. The overall rate of fecal incontinence was 3.9 %, abdominal pain was 47.4 %, constipation was 37.7 %, and diarrhea was 20.1 %. When comparing cancer types, there were no differences in pelvic floor symptoms.

Conclusion

Pelvic floor disorders are common in women with suspected gynecological malignancy at baseline before surgery. Recognizing pelvic floor disorders in the preoperative setting will allow for more individualized, comprehensive care for these women.

     

中医药与肿瘤基因表达

肿瘤从本质上是基因病.随着中医药治疗肿瘤效果在临床上的充分肯定和分子生物学的进展,从分子生物学的角度研究中医药抗肿瘤的机理成为一新的研究热点.本文围绕中医药对癌基因和抗癌基因的表达影响较全面地介绍近年来此领域的最新进展.     

HIV-1 infection alters CD4+ memory T-cell phenotype at the site of disease in extrapulmonary tuberculosis

HIV-1-infected people have an increased risk of developing extrapulmonary tuberculosis (TB), the immunopathogenesis of which is poorly understood. Here, we conducted a detailed immunological analysis of human pericardial TB, to determine the effect of HIV-1 co-infection on the phenotype of Mycobacterium tuberculosis (MTB)-specific memory T cells and the role of polyfunctional T cells at the disease site, using cells from pericardial fluid and blood of 74 patients with (n = 50) and without (n = 24) HIV-1 co-infection. The MTB antigen-induced IFN-γ response was elevated at the disease site, irrespective of HIV-1 status or antigenic stimulant. However, the IFN-γ ELISpot showed no clear evidence of increased numbers of antigen-specific cells at the disease site except for ESAT-6 in HIV-1 uninfected individuals (p = 0.009). Flow cytometric analysis showed that CD4+ memory T cells in the pericardial fluid of HIV-1-infected patients were of a less differentiated phenotype, with the presence of polyfunctional CD4+ T cells expressing TNF, IL-2 and IFN-γ. These results indicate that HIV-1 infection results in altered phenotype and function of MTB-specific CD4+ T cells at the disease site, which may contribute to the increased risk of developing TB at all stages of HIV-1 infection.     

Effect of <Emphasis Type="Italic">Citrullus vulgaris</Emphasis> on some functional indices of selected tissues of Wistar rats

Citrullus vulgaris (watermelon) is a fruit with prophylactic and therapeutic potentials. In an attempt to maximize these potentials, the seed and rind are now often consumed together with the pulp. This study aimed at evaluating the implications of such consumption. Study involved the use of 35 Wistar rats grouped into seven with a control group administered distilled water, and the other groups administered varying concentrations of the pulp and whole fruit for 28 days. Alanine and aspartate aminotransferase (ALT, AST) were assayed in the serum and liver. Total protein of the serum and selected tissues was determined and malondialdehyde (MDA) level measured. Phytochemical screening revealed the presence of steroids, saponin, alkaloids, flavonoids, and terpenoids in both whole fruit and pulp. Significant increases (p < 0.05) were seen in the liver ALT levels while there was a decreased (p < 0.05) intestinal total protein in the treatment groups. No significant (p ? 0.05) difference was seen in the serum and pancreas MDA levels while an increased (p < 0.05) intestinal MDA level was observed. Increased liver ALT levels in all the treatment groups might be due to high glutamate levels of C. vulgaris. Decreased (p ? 0.05) intestinal total protein might be indicative of protein loss, while elevated (p < 0.05) intestinal MDA levels in the groups administered whole fruit is suggestive of a defect in absorption at the intestinal epithelium. Hence, whole fruit consumption of C. vulgaris should be done with caution as it has potential to cause intestinal oxidative stress.     

Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training

Activation of the multifunctional Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca²⁺ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca²⁺ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature.