Lack of Mycobacterium leprae-specific uptake in Schwann cells

Among mycobacteria, Mycobacterium leprae have a unique property to infect peripheral nerves, which is the cause of a variety of debilities seen in leprosy. The possibility of selective uptake of M. leprae by Schwann cells was studied using a rat Schwannoma cell line 33B and rat sciatic nerve-derived Schwann cells. M. leprae were phagocytosed by 33B cells but so also were seven other mycobacteria ("Mycobacterium w," BCG, M. tuberculosis H37Rv, M. nonchromogenicum, M. vaccae, ICRC bacillus, and M. smegmatis) which do not involve peripheral nerves. All three mycobacteria tested (M. leprae, M. tuberculosis and "Mycobacterium w") were phagocytosed by sciatic nerve-derived Schwann cells. Both Schwannoma and Schwann cells phagocytosed even inert latex particles. These results fail to demonstrate any M. leprae-specific uptake system in Schwann cells.     

In-vitro binding of gonadotrophin to fish ovary

Binding of piscine and mammalian gonadotrophin to plasma membranes from the ovaries of a fish, the murrel (Channa punctatus), clearly suggests that the fish ovary possesses distinct and specific binding sites for both piscine and mammalian gonadotrophins. Maximum specific binding of 125I-labelled human chorionic gonadotrophin (125I-hCG) and 125I-labelled silver carp gonadotrophin (125I-scG) was obtained at 30 degrees C and pH 7.5 during 2 h of incubation. In competitive binding studies, binding of radiolabelled scG was effectively inhibited by piscine gonadotrophins while LH and hCG had less effect and FSH showed no inhibition. By using plasma membrane preparations from kidney, skeletal muscle, brain and ovary it could be shown that specific binding of radiolabelled gonadotrophins was restricted to ovarian tissue. Binding characteristics of both 125I-scG and 125I-hCG to a preparation of murrel ovarian plasma membranes showed saturability with high affinity and low capacity. Scatchard plot analysis gave a higher dissociation constant for hCG (Kd = 235 pmol/l) than for scG (Kd = 127 pmol/l). Maximum binding capacity of scG was about twofold higher (6.27 fmol/mg protein) than that of hCG (3.76 fmol/mg protein). An increase in gonadotrophin binding resulted in a greater formation of pregnenolone from cholesterol, indicating functional relevance. At a concentration of 8 mmol/l, Ca2+ markedly inhibited the binding of gonadotrophin. The physiological importance of this inhibition is discussed.     

Effect of aldrin on spermatogenesis, plasma gonadotrophins and testosterone, and testicular testosterone in the rat

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), mid-pachytene spermatocytes (mPSc) and step 7 spermatids (7Sd), along with radioimmunoassay of plasma gonadotrophins (FSH and LH), testosterone and testicular testosterone were performed in Wistar rats following treatment with aldrin (polycyclic chlorinated hydrocarbon insecticide) for approximately one (13 days) or two cycles (26 days) of the seminiferous epithelium. Extensive degeneration of all varieties of germ cells at stage VII, reduction in the sperm count and significant reductions in plasma concentrations of LH and testosterone were observed following aldrin treatment. The reduction in plasma concentrations of FSH was statistically significant only after treatment for two cycles. The inhibitory effect of aldrin on plasma gonadotrophins, testosterone levels, testicular testosterone content and numbers of 7Sd and ASg was maximum after treatment for two cycles. Administration of human chorionic gonadotrophin along with aldrin treatment for two cycles partially prevented the degeneration of germ cells and enhanced testosterone production. The results indicate that aldrin may have a direct inhibitory influence on gonadotrophin release, but the possibility of a direct action of the insecticide at the level of the testes is also discussed.     

A microscopic and immunodiagnostic search for giardiasis in patients with gastrointestinal disorders

Direct microscopy and an ELISA technique were used to determine the prevalence of Giardia lamblia and its antigen in stool samples from patients with Crohn's disease, ulcerative colitis, acute-onset diarrhoea, or dyspepsia. Cysts of Giardia lamblia were observed by microscopy of faeces from two of the patients with acute-onset diarrhoea and one with dyspepsia. Giardia antigen was detected in the faeces of five patients, including all three in whom cysts had been identified by microscopy. No evidence of giardiasis was found in any patient with Crohn's disease or ulcerative colitis. It is concluded that the ELISA can reliably distinguish giardiasis from a range of other gastrointestinal disorders.     

Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries

Elevation of lung capillary pressure causes exocytosis of the leukocyte adhesion receptor P-selectin in endothelial cells (ECs), indicating that lung ECs generate a proinflammatory response to pressure-induced stress. To define underlying mechanisms, we followed the EC signaling sequence leading to P-selectin exocytosis through application of real-time, in situ fluorescence microscopy in lung capillaries. Pressure elevation increased the amplitude of cytosolic Ca(2+) oscillations that triggered increases in the amplitude of mitochondrial Ca(2+) oscillations and in reactive oxygen species (ROS) production. Responses to blockers of the Ca(2+) oscillations and of mitochondrial electron transport indicated that the ROS production was Ca(2+) dependent and of mitochondrial origin. A new proinflammatory mechanism was revealed in that pressure-induced exocytosis of P-selectin was inhibited by both antioxidants and mitochondrial inhibitors, indicating that the exocytosis was driven by mitochondrial ROS. In this signaling pathway mitochondria coupled pressure-induced Ca(2+) oscillations to the production of ROS that in turn acted as diffusible messengers to activate P-selectin exocytosis. These findings implicate mitochondrial mechanisms in the lung's proinflammatory response to pressure elevation and identify mitochondrial ROS as critical to P-selectin exocytosis in lung capillary ECs.     

Morphology and histology of human and canine internal thoracic arteries.

BACKGROUND: We evaluated human and canine internal thoracic arteries (ITAs) to determine whether the latter is valid for studies relevant to clinical use. METHODS: We studied 19 human ITAs obtained from 1 female and 14 male victims of recent fatal accidents who had no evidence of cardiovascular disease (mean age = 39+/-19 years; range = 15 to 79 years), and ITAs of 21 randomly-selected mongrel dogs of both sexes, weighing 18-40 kg (average = 24.3+/-5.7 kg). Specimens were fixed in formalin at a controlled pressure of 120 mm Hg, before extensive assessment that included intimal thickening, condition of the internal elastic lamina, and number of medial elastic lamellae and vasa vasorum. RESULTS: The canine morphology and histology were similar to the human ITAs, but there was no intimal hyperplasia, and the media and adventitia were thinner (ITAs of humans older than 40 years had significant increases in medial thickness, as well as in overall length). Morphologically and histologically, the left and right canine ITAs were almost completely the same. CONCLUSIONS: Canine ITAs are valid for bilateral comparative studies and are a useful tissue source and model for clinically-relevant experimental studies.     

Plasmodium falciparum circumsporozoite protein: epidemiological variations among field isolates prevalent in India

Objective  To investigate the extent of genetic variations in T-helper-cell epitopic regions of circumsporozoite (CS) protein in Plasmodium falciparum field isolates collected from different regions of India at different phases of malaria transmission.
Methods  Genomic DNA was isolated from 507 P. falciparum wild-parasite isolates obtained from six geographical locations of India at three time points coinciding with malaria transmissions. The T-helper-cell epitopic regions were polymerase chain reaction (PCR)-amplified and the products were purified and then sequenced.
Results  Based on sequences, nine variants were found among isolates and they were categorized into nine groups (V-1 to V-9), where V-1 and V-2 were observed in all three time points (TP). The variants V-1 to V-4 in TP-1; V-1, V-2, V-5 to V-8 in TP-2; and V-1, V-2, V-5 and V-9 in TP-3 were present and they showed restricted heterogeneity. During peak transmission (TP-2), parasite populations were more diverse and heterogeneous and the variants regionally unbiased and restricted. However, the alleles of V-6 and V-9 in both Th2R and Th3R showed identical sequence variation with those observed in other geographical regions of the world. The remaining seven groups did not show such similarity.
Conclusion  The Th2R and Th3R epitopes are implicated in host immune response to P. falciparum . The polymorphism in these epitopic regions indicates antigenic diversity, which may cause adverse outcome of a subunit vaccine including the CS prototype variant. Therefore, the formulation of a vaccine considering the restricted local repertoire parasite populations may be helpful.     

Serum creatinine ratio: A novel predictor of mortality after percutaneous coronary intervention in patients with normal and abnormal renal function

The occurrence of contrast induced nephropathy (CIN) is associated with increased mortality after percutaneous revascularization procedures. However, the exact correlation between various levels of creatinine elevation relative to the baseline and subsequent mortality in patients with chronic renal insufficiency (CRI) is not well established. In addition, the relationship between elevated postprocedural creatinine and ensuing mortality in patients with normal baseline renal function needs to be investigated. Methods : All percutaneous coronary intervention (PCI) patients (n = 12,997) were analyzed for any rise in serum creatinine (SCr): CRI group (BSC ≥ 1.5 mg/dl) (n = 1,853) and normal baseline renal function (NBR BSC < 1.5 mg/dl) group (n = 11,144). Patients in each group were analyzed for any elevation in SCr postprocedure and subdivided based on the SCr ratio [peak SCr/Baseline creatinine (BSC)] of <1.25, 1.25–1.5, and >1.5. The overall incidence of CIN (defined as an increment of 25% over baseline creatinine) was 5.9%: 11.3% in the CRI group versus 5.1% in normal BSC group (P < 0.01). Recursive partitioning and Cox hazard modeling were used to assess significant variables associated with mortality within 1 year. Only serum creatinine ratio (SCrR) > 1.5 correlated with increased mortality in both CRI group as well as normal BSC group. Conclusions : SCrR > 1.5 predicts mortality at 1 year after PCI. The association between SCrR > 1.5 and increased mortality at follow‐up is observed in patients with CRI as well as normal baseline renal function. SCrR may thus serve as a useful clinical tool for risk stratification and prognostication of patients after PCI. © 2009 Wiley‐Liss, Inc.