Relaxin's induction of metalloproteinases is associated with the loss of collagen and glycosaminoglycans in synovial joint fibrocartilaginous explants

Diseases of specific fibrocartilaginous joints are especially common in women of reproductive age, suggesting that female hormones contribute to their etiopathogenesis. Previously, we showed that relaxin dose-dependently induces matrix metalloproteinase (MMP) expression in isolated joint fibrocartilaginous cells. Here we determined the effects of relaxin with or without β-estradiol on the modulation of MMPs in joint fibrocartilaginous explants, and assessed the contribution of these proteinases to the loss of collagen and glycosaminoglycan (GAG) in this tissue. Fibrocartilaginous discs from temporomandibular joints of female rabbits were cultured in medium alone or in medium containing relaxin (0.1 ng/ml) or β-estradiol (20 ng/ml) or relaxin plus β-estradiol. Additional experiments were done in the presence of the MMP inhibitor GM6001 or its control analog. After 48 hours of culture, the medium was assayed for MMPs and the discs were analyzed for collagen and GAG concentrations. Relaxin and β-estradiol plus relaxin induced the MMPs collagenase-1 and stromelysin-1 in fibrocartilaginous explants – a finding similar to that which we observed in pubic symphysis fibrocartilage, but not in articular cartilage explants. The induction of these proteinases by relaxin or β-estradiol plus relaxin was accompanied by a loss of GAGs and collagen in joint fibrocartilage. None of the hormone treatments altered the synthesis of GAGs, suggesting that the loss of this matrix molecule probably resulted from increased matrix degradation. Indeed, fibrocartilaginous explants cultured in the presence of GM6001 showed an inhibition of relaxin-induced and β-estradiol plus relaxin-induced collagenase and stromelysin activities to control baseline levels that were accompanied by the maintenance of collagen or GAG content at control levels. These findings show for the first time that relaxin has degradative effects on non-reproductive synovial joint fibrocartilaginous tissue and provide evidence for a link between relaxin, MMPs, and matrix degradation.     

Acetylhomocysteine thiolactone protection against phosphamidon-induced alteration of regional superoxide dismutase activity in the central nervous system and its correlation with altered lipid peroxidation.

Phosphamidon intoxication (2 mg/kg body wt./day for 7 days) inhibited SOD activity, but enhanced the lipid peroxidation in various CNS regions. Administration of cithiolone (8 mg/kg body wt./day, ip for 7 days), however, elevated SOD activity and depleted lipid peroxidation. Interestingly, no significant change was observed either in SOD activity or in lipid peroxidation following simultaneous administration of phosphamidon and cithiolone.     

Biological ability of Malpura rams to counter heat stress challenges and its consequences on production performance in a semi-arid tropical environment

A study was conducted to assess the biological ability of Malpura rams to counter heat stress challenges and its impact on the productive performance in a semi-arid tropical environment. The eighteen adult Malpura rams (average body weight 55.0 kg) were divided into two groups, GI (n = 9; Control) and GII (n = 9; heat stress). The study was conducted for a period of 60 days. The results showed that body weight, body condition score, heart girth and feed intake were significantly (p < 0.05) lower in GII as compared to GI rams. The physiological responses i.e. respiration rate, pulse rate, rectal temperature and sweating rate (body and scrotum) were significantly (p < 0.05) higher in rams exposed to heat stress. Among the endocrine parameters, plasma T₃, T₄ and testosterone concentrations were significantly (p < 0.05) lower in GII rams, while cortisol concentration was significantly (p < 0.05) higher in GII rams. In addition, heat stress significantly (p < 0.05) reduced semen volume, total sperm motility, sperm concentration and progressive sperm motility in GII rams. The results indicated that Malpura rams adapted to the heat stress condition, however, while doing so their production performances were compromised.     

Protein structure probed by polarization spectroscopy. II. A time-resolved fluorescence study of human fibrinogen

Human fibrinogen in solution was studied by monitoring the time-resolved depolarization of the fluorescence emitted by two spectroscopic labels of which the fluorescence lifetimes differ by an order of magnitude. Contrary to a long-held view, no evidence of molecular flexibility was found in the 10-1000 ns range. In addition, from the rate of the overall rotation, it is proposed that a prolate and symmetric ellipsoid of 47 X 10.5 nm may represent the time-averaged hydrodynamic size and shape of the protein in solution. This rigid and highly hydrated structure (4 g water/g protein) accommodates the latest nodular models obtained from electron microscopy, explains the singular hydrodynamics of fibrinogen and, apparently, it would perform the two main functions of the protein in haemostasis, blood coagulation and platelet aggregation, more efficiently than the flexible molecule.     

Biological functions as affected by summer season-related multiple environmental stressors (heat,nutritional and walking stress) in Malpura rams under semi-arid tropical environment

The study was conducted with the primary objective to establish the impact of simultaneously imposed multiple stressors (thermal, nutritional and walking) on various biological functions in Malpura rams. The study was conducted for a period of 45 days. Twenty adult Malpura rams (average BW 44.9 Kg) were used in the present study. The rams were divided into two groups, CON (n = 10; Control) and MS (n = 10; multiple stressors). Both body weight (p < 0.05) and body condition scoring (p < 0.01) were lower in MS compared with CON rams. All the scrotal measurements reduced significantly (p < 0.01) in MS rams. All the testicular measurements also reduced significantly (p < 0.01) in MS as compared to CON rams. The seminal attributes, individual motility (p < 0.05), rapid motility (p < 0.05) and curvilinear velocity (p < 0.05) were significantly reduced in CON rams. However, slowness (p < 0.05), linearity (p < 0.05) and straightness (p < 0.05) parameters significantly increased in MS as compared to CON rams. In addition, plasma testosterone concentration was lower (p < 0.05) in MS rams. The study established the impact of multiple stressors on growth and reproductive performance of Malpura rams. Further, the results revealed that the only semen quality was affected by multiple stressors, but the semen production remained intact between the groups, indicating the extreme adaptive capability of Malpura rams to hot semi-arid tropical environment.     

Miocene phosphorites from the Murray Ridge, northwestern Arabian Sea

Phosphorites from the Murray Ridge, NW Arabian Sea comprise nodules, bioclasts, and bone fragments. The nodules are made up of a homogeneous, light-colored phosphate nucleus consisting of Rivulariacean filamentous cyanobacteria and a thin dark-grey colored phosphate cortex showing abundant microbial filaments and microborings. The bioclasts comprise of  14–14.5 Ma old planktonic foraminifers, accepted as the time of deposition. Spherical to ovoid-shaped apatite microparticles resembling fossil bacteria are distinct components in the bioclasts. Bone fragments exhibit apatite fillings. The nodules and bone fragments consist entirely of carbonate fluorapatite (CFA) with low Al, K, and Th concentrations suggesting absence of continental detritus. Shale-normalized REE patterns of the samples support a seawater-derived composition. The highly uniform initial _Nd values of − 4.8 to − 5.1 are interpreted as the seawater value at the onset of phosphatization  14 Ma ago. In contrast, ⁸⁷Sr/⁸⁶Sr ratios show a large range of 0.709055 to 0.709124 corresponding to unusually young stratigraphic ages of  1 to 3 Ma. The data are interpreted as evidence for post-depositional Sr exchange of the recrystallizing phosphorites with fluids isotopically not much different from modern seawater. It is concluded that the phosphorites formed under oxic, shallow-water conditions where microbial populations assimilated phosphorus primarily from seawater and mediated precipitation of CFA during early diagenesis at the sediment–water interface on different substrates.