Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) alone and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopausal women undergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and 96 h after culture and progesterone, oestradiol and cAMP in media were measured by radioimmunoassays. FSH stimulated the accumulation of oestradiol from granulosa cells of small follicles during the follicular and luteal phases but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH. Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FSH and neither was affected by TNF. Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in granulosa cells from small follicles. FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH. However, FSH increased progesterone and cAMP secretion by granulosa cells obtained from large follicles during the follicular and luteal phases. During the luteal phase alone, TNF in combination with FSH increased progesterone accumulation above that of FSH alone. FSH did not increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained from large follicles during acyclicity. Thus, FSH increases progesterone, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol secretion specifically in those cells. In large follicles, FSH-stimulated granulosa cell secretion of oestradiol is limited to the follicular phase and this effect can be inhibited by TNF. In addition, when granulosa cells of large follicles do not increase oestradiol secretion in response to FSH, TNF stimulates progesterone secretion.     

Genetic variability in the humoral immune response to bovine herpesvirus-1 infection in dairy cattle and genetic correlations with performance traits

Bovine herpesvirus-1 (BoHV-1) is a viral pathogen of global significance that is known to instigate several diseases in cattle, the most notable of which include infectious bovine rhinotracheitis and bovine respiratory disease. The genetic variability in the humoral immune response to BoHV-1 has, to our knowledge, not ever been quantified. Therefore, the objectives of the present study were to estimate the genetic parameters for the humoral immune response to BoHV-1 in Irish female dairy cattle, as well as to investigate the genetic relationship between the humoral immune response to BoHV-1 with milk production performance, fertility performance, and animal mortality. Information on antibody response to BoHV-1 was available to the present study from 2 BoHV-1 sero-prevalence research studies conducted between the years 2010 to 2015, inclusive; after edits, BoHV-1 antibody test results were available on a total of 7,501 female cattle from 58 dairy herds. National records of milk production (i.e., 305-d milk yield, fat yield, protein yield, and somatic cell score; n = 1,211,905 milk-recorded cows), fertility performance (i.e., calving performance, pregnancy diagnosis, and insemination data; n = 2,365,657 cows) together with animal mortality data (i.e., birth, farm movement, death, slaughter, and export events; n = 12,853,257 animals) were also available. Animal linear mixed models were used to quantify variance components for BoHV-1 as well as to estimate genetic correlations among traits. The estimated genetic parameters for the humoral immune response to BoHV-1 in the present study (i.e., heritability range: 0.09 to 0.16) were similar to estimates previously reported for clinical signs of bovine respiratory disease in dairy and beef cattle (i.e., heritability range: 0.05 to 0.11). Results from the present study suggest that breeding for resistance to BoHV-1 infection could reduce the incidence of respiratory disease in cattle while having little or no effect on genetic selection for milk yield or milk constituents (i.e., genetic correlations ranged from ?0.13 to 0.17). Moreover, even though standard errors were large, results also suggest that breeding for resistance to BoHV-1 infection may indirectly improve fertility performance while also reducing the incidence of mortality in older animals (i.e., animals >182 d of age). Results can be used to inform breeding programs of potential genetic gains achievable for resistance to BoHV-1 infection in cattle.     

Heart rate variability: two eras of investigation

Changes in membrane potential are a regulatory signal for voltage-gated ion channels including the family of Ca2+ channels. This regulatory role includes the voltage-dependent opening, closing, and inactivation of ion channels and the control of drug access and affinity for discrete channels states. Membrane potential is both a short- and long-term regulatory signal controlling the number and function of these voltage-gated channels. Depolarization of neuronal and neurosecretory cells produces down-regulation of L-type voltage-gated Ca2+ channels. These processes are described and their relevance to physiologic and pathologic processes of neuronal development and neuroprotection are indicated.     

The ability of the rat to metabolize myristoyl-methionine: an acylamino acid with potentially useful antibacterial properties

Two experiments with Sprague Dawley rats tested their ability to hydrolyse myristoyl-methionine (M-M) into myristic acid and L-methionine (M). In the first experiment, lasting for 3 days. male rats were orally administered [9,10-3H]myristoyl-L-[35S]methionine. The recovery of radioactivity was approximately 90% for both isotopes; 19% of the administered 3H was recovered in the urine and 16% in the faeces, while the recovered 35S activity was 13 and 12%, respectively. The balance of the radioactivity was found among the tissues, organs and blood. In the second experiment, male and female rats received soybean-based diets which were supplemented with either 0.305% M-M or 0.2% M (both diets contained equal amounts of M) for periods up to 4 weeks. The growth rate of the rats receiving the 0.305% M-M diets was slightly slower than that for the rats on the 0.2% M diet, but the difference was not statistically significant (P > 0.05). The M-M rats had a transitory decrease in feed consumption, suggesting that palatability may have contributed to the growth difference and that a somewhat greater amount of M-M was necessary for the rat to attain the same growth rate as that produced by 0.2% M. When the amount of dietary M-M was increased to 3.05% M-M, a greater reduction in feed consumption and body weight gain was observed. This latter diet was an initial attempt to study the potential toxicity of M-M. None of the haematological, clinical chemistry or organ weight data suggested that M-M was overtly toxic per se, but longer-term feeding studies are needed to evaluate the potential toxicity of M-M more fully.     

Longitudinal changes in lung function associated with aspects of swine-confinement exposure

Several aspects of swine-confinement farming appear to be leading to adverse respiratory effects. This study was set up in a longitudinal design to study the association between certain characteristics of farms or the way they are run and a decline in lung function. A cohort of 171 pig farmers was observed for 3 years. Lung function was measured. Exposure to farm characteristics was determined at the start of the observation period, using data from standardized farm surveys and from diaries kept by the participants. Mean decline in lung function was 73 mL/year for forced expiratory volume in 1 second (FEV1) and 55 mL/year for forced vital capacity (FVC). A longitudinal decline in FEV1 was significantly associated with the use of quaternary ammonium compounds as disinfectants (an additional 43 mL/year) and also with the use of an automated dry feeding system (an additional 28 mL/year). The association with the use of wood shavings as bedding material was not statistically significant. The impact of these characteristics in a longitudinal study provides stronger evidence for causal inference than that shown in previous cross-sectional designs. This may be useful in promoting preventive measures.     

On the vanadium and tin contents of diet and human blood

The vanadium and tin contents of total diet samples collected in five Italian towns are given, and discussed in relation to literature data, their status as essential elements and their levels in human blood. Tin in blood was found to be below 2 ng ml-1 in a group of 14 subjects, and barely detectable even after oral consumption of 60 mg of tin.     

Hypoxia enhances [3H]noradrenaline release evoked by nicotinic receptor activation from the human neuroblastoma SH-SY5Y

We have used the human sympathetic neuronal line SH-SY5Y to investigate the effects of hypoxia on noradrenaline (NA) release evoked by either raised [K+]o (100 mM) or the nicotinic acetylcholine receptor (nAChR) agonist dimethylphenylpiperazinium iodide (DMPP). NA release was monitored by loading cells with [3H]NA and collecting effluent fractions from perfused cells kept in a sealed perifusion chamber. Cells were challenged twice with either stimulus and release was expressed as that evoked by the second challenge as a fraction of that evoked by the first. K+-evoked release was unaffected by hypoxia (PO2 approximately 30-38 mm Hg), but release evoked by DMPP was significantly increased. For both stimuli, replacement of Ca2+o with 1 mM EGTA abolished NA release. K+-evoked release was also dramatically reduced in the presence of 200 microM Cd2+ to block voltage-gated Ca2+ channels, but DMPP-evoked release was less affected. In hypoxia, DMPP-evoked Cd2+-resistant NA release was dramatically increased. Our findings indicate that hypoxia increases NA release evoked from SH-SY5Y cells in response to nAChR activation by increasing Ca2+ influx through the nAChR pore, or by activating an unidentified Cd2+-resistant Ca2+-influx pathway. As acetylcholine is the endogenous transmitter at sympathetic ganglia, these findings may have important implications for sympathetic activity under hypoxic conditions.     

The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.