Pressure-induced changes in the isometric contractions of single intact frog muscle fibres at low temperatures

Summary Effects of increased hydrostatic pressure (range 0.1–10 MPa) on isometric twitch and tetanic contractions of single intact muscle fibres, isolated from frog tibialis anterior muscle, were examined at 4–12° C. The tension changes produced on exposure to steady high pressures are compared with those produced on exposure to low concentrations of caffeine (0.5 mm, subthreshold for contracture) and when pressure is rapidly released during a contraction. The peak twitch tension was potentiated by pressure accompanied by increased rate of tension rise and increased duration; the pressure sensitivity of twitch tension was 8% mPa^-1. The correlation between the rate of tension rise and peak tension in caffeine-induced twitch tension potentiation was quantitatively similar to that in pressure-induced twitch potentiation. Experiments involving the rapid release of pressure (2 ms) during twitch contractions demonstrate that high pressure need only be maintained for a brief period during the early part of tension development to elicit full twitch potentiation. The tetanic tension was depressed by pressure (1% MPa^-1). Results demonstrate that the major effect of increased hydrostatic pressure on intact muscle fibres, which results in tension potentiation, is complete very early during contraction and is similar to that of caffeine.     

An investigation into the effects of ketoconazole on testicular function in Wistar rats

Ketoconazole was administered orally to sexually mature Wistar rats and testicular function assessed. A single oral dose of 24 mg ketoconazole/kg body weight lowered plasma testosterone and DHT levels by 83 and 50%, respectively within 2 h, without altering gonadotrophin levels. Treatment for up to 7 days decreased epididymal sperm number and motility and increased the proportion of abnormal sperm. The sperm appeared to be most affected 3 days after a single dose of ketoconazole and recovery had taken place by the seventh day. Daily treatment for up to 90 days also decreased sperm number and motility and increased the proportion of abnormal sperm, but did not affect testicular germ cells. No significant change was noted in the weights of the testis, epididymis, seminal vesicle and prostate; nor was there a change in testicular DNA, RNA and protein contents. Although fertility appeared to be impaired by long-term treatment, some of the treated rats mated successfully.     

Combined pharmacophore and 3D-QSAR study on a series of Staphylococcus aureus Sortase A inhibitors

Methicillin resistant Staphylococcus aureus has become a major health concern and it requires new therapeutic agents. Staphylococcus aureus Sortase A enzyme contributes in adherence of bacteria with the cell wall of host cell; consequently, inhibition of S. aureus Sortase A by small molecules could be employed as potential antibacterial agents against methicillin resistant S. aureus. Current study focused on the identification of 3D pharmacophoric features within a series of rhodanine, pyridazinone, and pyrazolethione analogs as S. aureus Sortase A inhibitors. Pharmacophore model was constructed employing representative molecules using Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database. The identified pharmacophoric points were then utilized to create alignment hypothesis for three-dimensional quantitative structure-activity relationships. Outcome of comparative molecular field analysis and comparative molecular similarity indices analysis experiments were in good agreement (comparative molecular field analysis: q(2) = 0.562 and r(2) = 0.995, comparative molecular similarity indices analysis: q(2) = 0.549 and r(2) = 0.978) and capable of explaining the variance in biological activities coherently with respect to the structural features of compounds. The results were also found in concurrence with the outcome of pharmacophoric features.     

Cellular Treatments for Spinal Cord Injury: The Time is Right for Clinical Trials

More than 1 million people in the United States live with a spinal cord injury (SCI). Despite medical advances, many patients with SCIs still experience substantial neurological disability, with loss of motor, sensory, and autonomic function. Cell therapy is ideally suited to address the multifactorial nature of the secondary events following SCI. Remarkable advances in our understanding of the pathophysiology of SCI, structural and functional magnetic resonance imaging, image-guided micro-neurosurgical techniques, and transplantable cell biology have enabled the use of cell-based regenerative techniques in the clinic. It is important to note that there are more than a dozen recently completed, ongoing, or recruiting cell therapy clinical trials for SCI that reflect the views of many key stakeholders. The field of regenerative neuroscience has reached a stage in which the clinical trials are scientifically and ethically justified. Although experimental models and analysis methods and techniques continue to evolve, no model will completely replicate the human condition. It is recognized that more work with cervical models of contusive/compressive SCI are required in parallel with clinical trials. It is also important that the clinical translation of advances made through well-established and validated experimental approaches in animal models move forward to meet the compelling needs of individuals with SCI and to advance the field of regenerative neuroscience. However, it is imperative that such efforts at translation be done in the most rigorous and informed fashion to determine safety and possible efficacy, and to provide key information to clinicians and basic scientists, which will allow improvements in regenerative techniques and the validation and refinement of existing preclinical animal models and research approaches. The field of regenerative neuroscience should not be stalled at the animal model stage, but instead the clinical trials need to be focused, safe, and ethical, backed up by a robust, translationally relevant preclinical research strategy.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-011-0076-7) contains supplementary material, which is available to authorized users.     

Quality of life issues for South Africans with acne vulgaris

The adverse effects of acne on the psyche have been established in patients from 'first world' countries. There has been no in depth study in predominantly black patients from Africa addressing this issue. This was a prospective cross-sectional study of acne patients attending a dermatology unit in KwaZulu-Natal, South Africa. A questionnaire was completed and acne graded by the Global Acne Grading scale. Psychological morbidity and quality of life (QOL) were assessed by the General Health Questionnaire and Dermatology Specific Quality of Life Questionnaires, respectively. We found that clinical severity was not associated with patient perception or psychological distress. The QOL measures such as feelings, social activities, performance at work or school, activities of daily living and overall mental health were found to be associated with distress with associated P-values of 0.0002, 0.0168, 0.0032, 0.033 and < 0.0001, respectively. The severity of acne was not associated with psychological distress. Painful and bleeding lesions were associated with distress levels; P = 0.042 and P = 0.019, respectively. In conclusion, South African patients with acne vulgaris suffer significant psychological distress, which affects the quality of their lives.     

Massive cryptococcal lymphadenopathy in an immunocompetent pregnant patient

Isolated pulmonary cryptococcosis remains a rare entity among pregnant or parturient patients who are immunocompetent, with few documented cases in the literature. We report a case of massive mediastinal lymphadenopathy in an immunocompetent pregnant patient with isolated pulmonary cryptococcosis. The unusual radiographic presentation of the present case merits special emphasis. Cryptococcal lymphadenopathy has a low prevalence in immunocompetent hosts and is more usually associated with an immunocompromised status. The occurrence of massive cryptococcal lymphadenopathy in an immunocompetent host is rare with previously reported cases occurring in non-pregnant patients.     

Comparison of plain chest radiography and high-resolution CT in human immunodeficiency virus infected patients with community-acquired pneumonia: a sub-Saharan Africa study

The objective of the study was to determine the proportion of patients with missed lesions on plain chest radiographs compared with high-resolution computed tomography (HRCT) in 49 human immunodeficiency virus (HIV) infected patients with community-acquired pneumonia (CAP). Patients underwent plain chest radiography and HRCT scans of the chest at admission. Microbiological investigations for CAP were performed. An experienced radiologist, without knowledge of clinical or pathological data, reported the chest radiographs and HRCT scans. The study group included 26 females and 23 males, aged 18-53 years (mean age 36 years). Organisms were isolated from 26 patients (53%). In 40 patients (82%), the HRCT scans demonstrated lesions not visualized on the plain chest radiographs. There was 100% correlation between plain radiographic and HRCT scan findings in nine cases (18%). Lesions that were not visualized on the plain radiographs but elucidated on HRCT included: pleural effusion (n = 14), ground-glass opacification (n = 20), pericardial effusion (n = 8), cavitation (n = 4), cysts (n = 4), bullae (n = 4), abscess (n = 1) and pneumothorax (n = 1). In 20 of 23 cases, hilar lymphadenopathy, identified on HRCT, was not recognized on plain chest radiographs. In patients in whom an organism was isolated, a correct HRCT diagnosis of pulmonary tuberculosis, bacterial pneumonia and Pneumocystis carinii pneumonia (PCP) was made in 80%, 84% and 100% of cases, respectively. The proportion of patients with missed lesions on plain chest radiographs in HIV infected patients with CAP was high. This has important implications for management and prognosis. HRCT scans correlate well with the microbiological diagnosis when reported by an experienced radiologist.