Creatine phosphokinase and aspartate aminotransverase profiles and its relation to the severity of uterine torsion in Egyptian buffalo

Thirty-five female buffalo suffering from uterine torsion were brought to the veterinary clinic and were clinically examined as well as monitored using trans-rectal and trans-abdominal ultrasonography. Three blood samples were taken from each animal (before re-torsion, 1h and 24h after delivery) to investigate the relationship between the serum concentrations of creatine phosphokinase (CPK), aspartate aminotransverase (AST) and the severity of uterine torsion. The incidence of uterine torsion was greater in multiparous than young buffalo. The concentration of CPK and AST showed a significant (P<0.05) increase with increased duration and severity of uterine torsion. However, the concentration of CPK was less in the cases delivering a live foetus than a dead one. Animals with CPK above 450 IU usually had uterine rupture during labour (85.7%) and CPK level above 500 U/l did not respond to treatment. After labour, the AST concentration reached normal in some cases (1-6 and 24-48h). Animals with AST above 100 U/l may be either not respond to the re-torsion procedures or respond but exposed to uterine rupture during vaginal delivery. Occurrence of the uterine torsion is usually accompanied by an elevation (P<0.05) of AST concentration regardless the degree, position and viability of the foetus (76.47-100.25 U/l vs. 59.43 U/l). Animals with severe torsion or carrying a dead foetus had greater (P<0.05) AST compared to those having a mild degree or carrying live foetus. After labour, the concentration of AST decreased (P<0.05) but never reached normal concentrations up to 24h except in animals having a live foetus. In conclusion, concentration of CPK and AST can be used as a prognostic indicator for the occurrence of uterine torsion in Egyptian buffalo.     

Mice Lacking Major Brain Gangliosides Develop Parkinsonism

Parkinson’s disease (PD) is the second most prevalent late-onset neurodegenerative disorder that affects nearly 1% of the global population aged 65 and older. Whereas palliative treatments are in use, the goal of blocking progression of motor and cognitive disability remains unfulfilled. A better understanding of the basic pathophysiological mechanisms underlying PD would help to advance that goal. The present study provides evidence that brain ganglioside abnormality, in particular GM1, may be involved. This is based on use of the genetically altered mice with disrupted gene Galgt1 for GM2/GD2 synthase which depletes GM2/GD2 and all the gangliotetraose gangliosides that constitute the major molecular species of brain. These knockout mice show overt motor disability on aging and clear indications of motor impairment with appropriate testing at an earlier age. This disability was rectified by L-dopa administration. These mice show other characteristic symptoms of PD, including depletion of striatal dopamine (DA), loss of DA neurons of the substantia nigra pars compacta, and aggregation of alpha synuclein. These manifestations of parkinsonism were largely attenuated by administration of LIGA-20, a membrane permeable analog of GM1 that penetrates the blood brain barrier and enters living neurons. These results suggest that perturbation of intracellular mechanisms mediated by intracellular GM1 may be a contributing factor to PD.     

3-Hydrogenkwadaphnin targets inosine 5'-monophosphate dehydrogenase and triggers post-G1 arrest apoptosis in human leukemia cell lines

3-Hydrogenkwadaphnin (3-HK) is a recently characterized daphnane-type compound isolated from Dendrostellera lessertii with high anti-tumor activity in animal models. Herein, we report on time- and dose-dependent effects of this compound on growth, differentiation, IMPDH inhibition, cell cycle and apoptosis of a panel of human leukemia cell lines (HL-60, K562 and Molt4). The drug decreased the growth of leukemia cells in less than 24 h of treatment. However, longer exposure times and/or higher concentrations were required to promote cell apoptosis. Cell cycle analysis revealed the accumulation of cells in their G1 phase as early as 12 h after drug exposure but sub-G1 population was recorded after 24 h. Occurrence of apoptosis was constantly accompanied by morphological (staining with DNA-binding dyes) and biochemical (DNA fragments) variations among drug-treated cells. Despite these observations, non-activated normal human PBL were insensitive to the drug action. In addition, treatment of PHA-activated PBL, K562, Molt4 and HL-60 cells with a single dose of the drug for 24 h led to the inhibition of IMPDH activity by almost 37, 38, 44 and 50%, respectively. In contrast, no difference in IMPDH activities were seen between normal PBL and the drug treated PBL cells. Restoration of the depleted GTP concentration by exogenous addition of guanosine (25-50 microM) reversed the drug effects on cell growth, DNA fragmentation and apoptosis. Furthermore, the drug effects were potentiated by exogenous addition of hypoxanthine to the drug-treated cells. Reduction of the drug potency on the non-proliferative (retinoic acid treated) HL-60 cells by almost 40%, compared to the proliferative cells, clearly shows type II IMPDH as one of the main targets of the drug. These results suggest that 3-HK may be a powerful candidate for treatment of leukemia.     

Association of Flavobacterium psychrophilum strains with intestinal explants of rainbow trout Oncorhynchus mykiss

Flavobacterium psychrophilum is an important pathogen in rainbow trout Oncorhynchus mykiss. The portal of entry for F. psychrophilum is not well known. In this study, the role of the intestine as a colonization site for F. psychrophilum was determined. For this purpose, the ability of a high (Dubois) and a low (99/10A) virulence strain of F. psychrophilum to adhere to intestinal explants of rainbow trout was evaluated. After incubation, samples of the gut were examined bacteriologically, histologically and by electron microscopy. The number of gut-associated F. psychrophilum bacteria was significantly higher for the Dubois than for the 99/10A strain. Histological samples clearly showed numerous bacteria of the high virulence strain associated with the intestinal tissue as opposed to only a few bacteria of the low virulence strain. Additionally, extensive exfoliation of intestinal epithelium was noted after incubation with the high virulence strain, but less with the low virulence strain. These findings were confirmed using scanning electron microscopy and suggest that the intestinal epithelium might represent an important site for colonization of the F. psychrophilum strain and may act as a portal of entry for high virulence F. psychrophilum.     

Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer

Cancer is the second leading cause of death worldwide. Conventional therapies cause serious side effects and, at best, merely extend the patient's lifespan by a few years. Cancer control may therefore benefit from the potential that resides in alternative therapies. There is thus an increasing demand to utilize alternative concepts or approaches to the prevention of cancer. In this report, we show a potential protective effect of Fenugreek seeds against 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced breast cancer in rats. At 200 mg/kg b.wt., Fenugreek seeds' extract significantly inhibited the DMBA-induced mammary hyperplasia and decreased its incidence. Epidemiological studies also implicate apoptosis as a mechanism that might mediate the Fenugreek's anti-breast cancer protective effects. To our knowledge, this is the first study that suggests significant chemopreventive effects of Fenugreek seeds against breast cancer.     

Comparison of 3D dynamic virtual model to link segment model for estimation of net L4/L5 reaction moments during lifting

The purpose of this study was to validate a 3D dynamic virtual model for lifting tasks against a validated link segment model (LSM). A face validation study was conducted by collecting x, y, z coordinate data and using them in both virtual and LSM models. An upper body virtual model was needed to calculate the 3D torques about human joints for use in simulated lifting styles and to estimate the effect of external mechanical devices on human body. Firstly, the model had to be validated to be sure it provided accurate estimates of 3D moments in comparison to a previously validated LSM. Three synchronised Fastrak units with nine sensors were used to record data from one male subject who completed dynamic box lifting under 27 different load conditions (box weights (3), lifting techniques (3) and rotations (3)). The external moments about three axes of L4/L5 were compared for both models. A pressure switch on the box was used to denote the start and end of the lift. An excellent agreement [image omitted] was found between the two models for dynamic lifting tasks, especially for larger moments in flexion and extension. This virtual model was considered valid for use in a complete simulation of the upper body skeletal system. This biomechanical virtual model of the musculoskeletal system can be used by researchers and practitioners to give a better tool to study the causes of LBP and the effect of intervention strategies, by permitting the researcher to see and control a virtual subject's motions.     

Combining Peripheral Nerve Grafting and Matrix Modulation to Repair the Injured Rat Spinal Cord

Traumatic injury to the spinal cord (SCI) causes death of neurons, disruption of motor and sensory nerve fiber (axon) pathways and disruption of communication with the brain. One of the goals of our research is to promote axon regeneration to restore connectivity across the lesion site. To accomplish this we developed a peripheral nerve (PN) grafting technique where segments of sciatic nerve are either placed directly between the damaged ends of the spinal cord or are used to form a bridge across the lesion. There are several advantages to this approach compared to transplantation of other neural tissues; regenerating axons can be directed towards a specific target area, the number and source of regenerating axons is easily determined by tracing techniques, the graft can be used for electrophysiological experiments to measure functional recovery associated with axons in the graft, and it is possible to use an autologous nerve to reduce the possibility of graft rejection. In our lab we have performed both autologous (donor and recipient are the same animal) and heterologous (donor and recipient are different animals) grafts with comparable results. This approach has been used successfully in both acute and chronic injury situations. Regenerated axons that reach the distal end of the PN graft often fail to extend back into the spinal cord, so we use microinjections of chondroitinase to degrade inhibitory molecules associated with the scar tissue surrounding the area of SCI. At the same time we have found that providing exogenous growth and trophic molecules encourages longer distance axonal regrowth into the spinal cord. Several months after transplantation we perform a variety of anatomical, behavioral and electrophysiological tests to evaluate the recovery of function in our spinal cord injured animals. This experimental approach has been used successfully in several spinal cord injury models, at different levels of injury and in different species (mouse, rat and cat). Importantly, the peripheral nerve grafting approach is effective in promoting regeneration by acute and chronically injured neurons.Download video file.^{(224M, mp4)}