Acute and sub-acute effects of 2-butenoic acid-3-(diethoxy phosphinothioyl) methyl ester (RPR-II) on testis of albino rat

Acute and sub-acute toxic effects of a novel phosphorothionate coded as RPR-II on testis of albino rats were studied. In acute study rats received a single dose of 12.3 mg/kg of RPR-II and sacrificed after 24 hr. For sub-acute study 0.58 mg/kg/day was administered orally to rats for 10 and 21 days. Acute exposure of rats to RPR-II brought no change either in the gonadosomatic index (GSI) or in the structure of testis or in the serum levels of testosterone. Testis glutathione (GSH) level and glutathione S-transferase (GST) activity was significantly decreased whereas, acid phosphatase (AcP) levels increased significantly at 24 hr post-treatment. On 7th day (withdrawal period) after the cessation of the treatment the GSH, GST, AcP, and AkP levels reached to near control. The sub-acute study revealed a significant decrease in GSI on 10th and 21st day of the treatment. In contrast, a time-dependent and significant increased in GSH level and GST activity was observed on 100th and 21st day of post-treatment, except GSH level on 10th day, which was declined. Due to RPR-II treatment the testis AcP and alkaline phosphatase (AkP) levels were significant at both 10th and 21st day of medication but AcP levels were increased whereas AkP levels decreased. The histopathological studies on day 10th showed considerable loss of spermatozoids in testis and at 21st day complete derangement of cellular organization was observed. Testosterone levels decreased significantly on 10th day and remained significantly low at 21st day. However, withdrawal studies showed a recovery in testis of rat treated with RPR-II. GST, GSH, GSI, AcP and AkP values recovered, testosterone levels were also well recovered but recovery in testis structure remained at a low profile. The present study suggests that RPR-II may cause testicular toxicity in rats affecting the normal functioning of testis and it also gave some new information in withdrawal studies.     

Neutrophil activation by bacterial lipoprotein versus lipopolysaccharide: differential requirements for serum and CD14

Neutrophil activation plays an important role in the inflammatory response to Gram-negative bacterial infections. LPS has been shown to be a major mediator of neutrophil activation which is accompanied by an early down-regulation of L-selectin and up-regulation of CD1lb/CD18. In this study, we investigated whether lipoprotein (LP), the most abundant protein in the outer membrane of bacteria from the family Enterobacteriaceae, can activate neutrophils and whether this activation is mediated by mechanisms that differ from those used by LPS or Escherichia coli diphosphoryl lipid A (EcDPLA). Neutrophil activation was assessed by measuring down-regulation of L-selectin and up-regulation of CD11b/CD18. When comparing molar concentrations of LP vs EcDPLA, LP was more potent (four times) at activating neutrophils. In contrast to LPS/EcDPLA, LP activation of neutrophils was serum independent. However, LP activation of neutrophils was enhanced by the addition of soluble CD14 and/or LPS-binding protein. In the presence of serum, LP activation of neutrophils was inhibited by different mAbs to CD14. This inhibition was significantly reduced or absent when performed in the absence of serum. Diphosphoryl lipid A from Rhodobacter spheroides (RaDPLA) completely inhibited LPS/EcDPLA activation of neutrophils but only slightly inhibited LP activation of neutrophils. These results suggest that LP activation of human neutrophils can be mediated by a mechanism that is different from LPS activation and that LP is a potentially important component in the development of diseases caused by Gram-negative bacteria of the family Enterobacteriaceae.     

Effect of ninhydrin on the biochemical and histopathological changes induced by ethanol in gastric mucosa of rats

Studies on the effect of ninhydrin in the normal gastric mucosa and against the ethanol induced gastric injury were undertaken in rats in view of the presence of a carbonyl function as well as hydroxyl groups in its chemical structure. In spite of its potentials to generate hydroxyl radicals, it is deemed to possess antioxidant property by virtue of its electrophilic nature. Recent studies have shown gastro-protection to mediate through a reaction between the electrophilic compounds and sulfhydryl groups of the mucosa. Hence it was found worthwhile to evaluate the interaction between the oxidant and antioxidant functions in the structure of the same compound. The effects of ninhydrin pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2M NaOH were investigated in rats. The gastric tissue in ethanol-treated rats was analyzed for different histopathological lesions. In addition, the effects on ethanol-induced changes in the gastric levels of proteins, nucleic acids, non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also evaluated. Ninhydrin, as such, failed to induce any significant changes in normal gastric mucosa, while its pretreatment at oral doses of 5, 10 and 20 mg/kg was found to provide a dose-dependent protection against the ulcers induced by ethanol, NaOH and NaCl. The results of histopathological evaluation revealed a protective effect of ninhydrin on congestion, hemorrhage, edema, erosions and necrosis caused by ethanol. Furthermore, the pretreatment afforded a dose-dependent inhibition of the ethanol-induced depletion of proteins, nucleic acids, NP-SH and increase of MDA in the gastric tissue. The results obtained clearly demonstrate the anti-ulcerogenic activity of ninhydrin. The exact mechanism of action is not known. However, the carbonyl function in ninhydrin appears to achieve antioxidant balance and protect the gastric mucosa from the ethanol-induced gastric injury. Further studies are warranted to investigate the toxicity and detailed mechanism of action of this potent compound before any clinical trials, especially at the effective lower doses.     

Calculation of chromophore excited state energy shifts in response to molecular dynamics of pigment-protein complexes

The absorption and energy transfer properties of photosynthetic pigments are strongly influenced by their local environment or “site.” Local electrostatic fields vary in time with protein and chromophore molecular movement and thus transiently influence the excited state transition properties of individual chromophores. Site-specific information is experimentally inaccessible in many light-harvesting pigment–proteins due to multiple chromophores with overlapping spectra. Full quantum mechanical calculations of each chromophores excited state properties are too computationally demanding to efficiently calculate the changing excitation energies along a molecular dynamics trajectory in a pigment–protein complex. A simplified calculation of electrostatic interactions with each chromophores ground to excited state transition, the so-called charge density coupling (CDC) for site energy, CDC, has previously been developed to address this problem. We compared CDC to more rigorous quantum chemical calculations to determine its accuracy in computing excited state energy shifts and their fluctuations within a molecular dynamics simulation of the bacteriochlorophyll containing light-harvesting Fenna–Mathews–Olson (FMO) protein. In most cases CDC calculations differed from quantum mechanical (QM) calculations in predicting both excited state energy and its fluctuations. The discrepancies arose from the inability of CDC to account for the differing effects of charge on ground and excited state electron orbitals. Results of our study show that QM calculations are indispensible for site energy computations and the quantification of contributions from different parts of the system to the overall site energy shift. We suggest an extension of QM/MM methodology of site energy shift calculations capable of accounting for long-range electrostatic potential contributions from the whole system, including solvent and ions.     

Dietary zinc-methionine enhances mononuclear-phagocytic function in young turkeys

The ability of dietary zinc-methionine (Zn-Met) to enhance mononuclear-phagocytic function againstSalmonella arizona andenteritids was investigated in young turkeys. Feed/gain and body wt gain at 21 d of age were not affected by Zn-Met. The addition of 30 or 45 ppm Zn from Zn-Met to a Zn adequate diet significantly increased cutaneous basophil hypersensitivity to phytohemagglutinin-P. The clearance of intravenously administeredS. enteritidis from blood was not affected by 30 ppm of supplemental Zn from Zn-Met. However, 30 ppm Zn from Zn-Met increased the reduction of intravenously administeredS. arizona from spleen. Percentages of myeloid and mononuclear-phagocytic cells before and afterS. enteritidis infection were not affected by supplemental Zn-Met. Turkeys supplemented with Zn-Met showed enhanced in vitro phagocytosis ofS. enteritidis by Sephadex-elicited abdominal exudate cells. The phagocytosis ofS. arizona was unaffected by Zn-Met.     

Efficacy of triclabendazole against fascioloidiasis (Fascioloides magna) in naturally infected white-tailed deer (Odocoileus virginianus)

The efficacy of triclabendazole was evaluated in the treatment of naturally acquired Fascioloides magna infections in white-tailed deer (Odocoileus virginianus). Twenty white-tailed deer were captured on the Welder Wildlife Refuge (Sinton, San Patricio County, Texas, USA) and maintained in a 64 x 64 m deer enclosure. Ten deer were given a 5% suspension of triclabendazole orally at a dosage of 10 mg/kg body weight and 10 deer were given a placebo. Three wk later the deer were euthanized and examined for parasites. At necropsy 19 deer were infected. All specimens of F. magna from the tissues of the triclabendazole treated deer were dead or severely affected by the drug as indicated by changes in their size, color, movement and texture relative to those from control deer. The drug was considered 100% effective against this parasite. Adverse reactions of the deer to the drug were not observed.     

Chicken developmental antigens in 15I5-B-congenic lines

Six partially developed 15I5-B-congenic lines of chickens were used to assess the genetic influence on the developmental expression of selected epitopes of two avian developmental antigen systems: chicken fetal antigen (CFA) and chicken adult antigen (CAA). Both CFA and CAA are serologically and molecularly complex hematopoietic antigen systems, yet little is known about genetic influences on their expression. Using polyclonal rabbit anti-CFA, only slight variations in overall CFA expression on peripheral erythrocytes were observed during neonatal development; no consistent trend was evident. In contrast, analysis with monoclonal antibody 10C6 revealed that the incidence of CFA determinant 8 (CFA8) on erythrocytes of the early neonate was significantly reduced in line 15I5 compared with lines .6-2, .7-2 and .15I-5; line .C-12 also exhibited a reduced CFA8 incidence at hatching. Likewise, the CAA epitope detected by monoclonal antibody 3F12 was found to appear at a slower rate on erythrocytes from lines 15I5 and .C-12 than on those of other lines. Similar results were obtained using the anti-CAA monoclonal 4C2 where reduced expression was found in lines 15I5, .C-12, and .P-13. Results of complement-mediated cytolysis using the positive control 9F9 monoclonal antibody suggested that observed genetic differences were not due to inherent differences in erythroid cytolytic sensitivity. Neither could the results be explained by the incidence of circulating reticulocytes vs. mature erythrocytes within the lines. Rather, the results suggest that different genetic lines of chickens vary in the developmental kinetics of definitive erythrocyte subpopulations bearing specific phenotypes defined by monoclonal antibodies. These findings are discussed in light of previous observations using these B-congenic lines.     

Timeline: Raising the profile of genetics in primary care

Primary care practitioners recognize that genetics is relevant to their daily practice, for example, for detecting and managing the risk of multifactorial disorders and genetic reproductive risks, and, in future, for targeted drug therapy. However, they lack confidence in their ability to apply genetic approaches. In fact, genetics is already ingrained in current practice, and the development of appropriate guidelines and web-based information resources will help practitioners to make personalized genetic risk assessment a part of holistic, patient-oriented primary health care.