Early detection of subclinical mastitis in lactating dairy cows using cow-level features.

Subclinical mastitis in cows affects their health, well-being, longevity, and performance, leading to reduced productivity and profit. Early prediction of subclinical mastitis can enable dairy farmers to perform interventions to mitigate its effect. The present study investigated how well predictive models built using machine learning techniques can detect subclinical mastitis up to 7 d before its occurrence. The data set used consisted of 1,346,207 milk-day (i.e., a day when milk was collected on both morning and evening) records spanning 9 yr from 2,389 cows producing on 7 Irish research farms. Individual cow composite milk yield and maximum milk flow were available twice daily, whereas milk composition (i.e., fat, lactose, protein) and somatic cell count (SCC) were collected once per week. Other features describing parity, calving dates, predicted transmitting ability for SCC, body weight, and history of subclinical mastitis were also available. The results of the study showed that a gradient boosting machine model trained to predict the onset of subclinical mastitis 7 d before a subclinical case occurs achieved a sensitivity and specificity of 69.45 and 95.64%, respectively. Reduced data collection frequency, where milk composition and SCC were recorded only every 15, 30, 45, and 60 d was simulated by masking data, to reflect the frequency of recording of this data on commercial dairy farms in Ireland. The sensitivity and specificity scores reduced as recording frequency reduced with respective scores of 66.93 and 80.43% when milk composition and SCC were recorded just every 60 d. Results demonstrate that models built on data that could be recorded routinely available on commercial dairy farms, can achieve useful predictive ability of subclinical mastitis even with reduced frequency of milk composition and SCC recording.

A new method for the production of experimental diabetes in rabbits.

Oral administration of 250 mg hydrochlorothiazide/kg, with previous i.v. injection of 4 i.u. soluble insulin or s.c. injection of protamine-zinc insulin, has been found to produce stable hyperglycaemia in rabbits irrespective of sex. It is thought that insulin helps the selective action of hydrochlorothiazide on the beta cells by removing the protective glucose barrier. Although stimulation of glucagon or some extra-pancreatic mechanism at the initial stage could not be altogether ruled out, the central action of the drug is supported by the finding that the hydrochlorothiazide-induced hyperglycaemia was lowered by the sulphonylurea derivative, chlorpropamide.

Modulation of luteinizing hormone receptors: effect of an inhibitor of prolactin secretion, p-coumaric acid.

Daily oral administration of p-coumaric acid (PCA) at a dose of 50 mg/kg body wt for 21 days to adult male mice caused a dramatic reduction in serum prolactin concentrations. A significant fall in testicular LH binding was also observed after PCA treatment. Complete recovery of testicular LH binding was obtained by daily administration of prolactin (500 micrograms/mouse) when given simultaneously from day 9 of PCA treatment. A lower daily dose of prolactin (250 micrograms) was found to be ineffective. Scatchard analysis of binding data suggested a decrease in the number of testicular LH binding sites after PCA treatment whereas the affinity constant was unchanged. These results provide direct evidence for an inhibitory effect of PCA on prolactin secretion and also provide additional evidence in favour of a role of prolactin in the modulation of LH receptors.

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.

Antifertility effect of chronically administered Malviscus conzattii flower extract on fertility of male rats.

Quantitative evaluation of different varieties of germ cells at stage VII of the cycle, namely type A spermatogonia, pre-leptotene spermatocytes, mid-pachytene spermatocytes, step 7 and step 19 spermatids, along with radio-immunoassay of serum gonadotrophins (LH and FSH), testosterone and testicular testosterone were performed in rats of Wistar strain following treatment with methanolic extract of flowers of Malvaviscus conzattii (MVC) at a dose level of 800 mg/kg b.w. for 30 consecutive days. The treatment period just exceeds two cycles of the seminiferous epithelium of the Wistar strain rats (one cycle is 13.2 days). Reduction of step 7 and 19 spermatids at stage VII were observed. Significant reduction in serum concentration of LH and testosterone were observed three and four weeks after treatment. Testicular testosterone was also reduced. No distinct change in serum FSH concentration was recorded. The results indicate that the extract may have an inhibitory influence on gonadotrophin release which may be held responsible for the decline in testosterone production, leading to change in spermatogenesis caused by the MVC extract. Replacement with hCG along with MVC prevented degeneration of step 7 and step 19 spermatids, and enhanced testosterone production support the same idea.

Antifertility efficacy of the plant Aristolochia indica linn on mouse.

Two compounds isolated from the alcoholic extract of the roots of Aristolochia indica Linn were tested on day 6 pregnant mice. One of the compounds, p-coumaric acid showed 100% interceptive activity at the single oral dose of 50 mg/kg of body weight. The antifertility efficacy of these two compounds is discussed.

Antifertility effects of the steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol 3-monobenzoate on mice.

The steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol 3-monobenzoate at a dose of 40 mg/kg of body weight has 100% interceptive activity when administered orally in a single dose during 6-7 days of gestation but it has no action on pregnancy if treated on 10th, 13th or 16th day of pregnancy. The interceptive activity of the steroid is lost by simultaneous injection of prolactin, progesterone or LH.

Biological profile of the steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol-3-monobenzoate.

The steroid 5 alpha-stigmastane-3 beta, 5, 6 beta-triol-3-monobenzoate at a dose of 40 mg/kg/day showed significant antifertility activity when administered orally in a single or in consecutive doses during pre-implantation stage of pregnancy in mice. In the rabbit interceptive activity was obtained when the test steroid was administered on Day 8 of pregnancy in a single dose level. The compound failed to show any distinct estrogenic or androgenic property following bioassay method. But in McPhial test, the compound showed some progestagenic activity.

Changes in uterine phosphatase levels in mice treated with aristolic acid during early pregnancy.

Aristolic acid (AA) exerted interceptive activity in mice. A single oral dose of aristolic acid at the dose levels of 120 and 90 mg/kg on Day 1 or Day 6 of pregnancy in mouse resulted in a rise of acid phosphatase (AP) and fall of alkaline phosphatase (ALP) and protein in uterus in both groups. Both delta 5-3 beta-hydroxy-steroid dehydrogenase (delta 5-3 beta-HSD) and glucose 6-phosphate-dehydrogenase (G6PD) of ovaries remained unaltered. Exogenous progesterone (1 mg s.c., Days 5-8) administered along with aristolic acid (on Day 6 only) could neither protect pregnancy nor prevent the biochemical changes produced in the uterus due to drug treatment. This unaltered steroidogenesis and alteration in alkaline phosphatase, acid phosphatase and protein gives some insight into the mechanism of action of the compound aristolic acid.

3-(4-hydroxy phenyl)-2-propenoic acid - a reproductive inhibitor in male rat.

Oral administration of 3-(4-hydroxy phenyl)-2-propenoic acid, at a dose of 50 mg/kg body weight/day (reported antiprolactin dose in rat) for 56 days, to adult male rat produces complete loss of libido, significant decrease in weight of testis and accessory sex organs, decrease in fructose content of coagulating gland and reduction in acid phosphatase activity in prostate. All these effects can be reversed by exogenous prolactin (500 micrograms/rat/day) plus testosterone propionate (200 micrograms/rat/day), but not by prolactin or testosterone alone, when administered along with the test compound for the last 28 days. Inhibitory influence of the compound over the reproductive organs is believed to be attributed primarily to the antiprolactin nature of the compound and secondarily to the significant (P less than 0.01) fall in plasma testosterone level caused by the compound.

A probe into the possible mechanism underlying the interceptive action of aristolic acid.

Oral administration of aristolic acid (90 mg/kg body weight) on day 6 pregnant and pseudopregnant mice resulted in the termination of pregnancy with in utero fetal death but the length of pseudopregnancy remained unaffected. Peripheral level of progesterone remained statistically uninfluenced in both conditions and exogenous progesterone failed to prevent aristolic acid-induced pregnancy loss, both of which rule out the involvement of luteolysis as the causal factor for the termination of pregnancy. In another experiment, aristolic acid was found to have no inhibitory effect over the maintenance of decidual cell reaction which indicates no inhibitory influence of the compound on uterine utilization of progesterone but points to the fact that presence of concepts is an essential component in the array of mechanism(s) leading to the termination of pregnancy. Probable toxic effect of aristolic acid on the concepts is discussed.

Disruption of pregnancy in mouse by aristolic acid: I. Plausible explanation in relation to early pregnancy events.

Aristolic acid (AA), obtained from Aristolochia indica Linn, disrupted nidation in mice when administered on Day 1 of pregnancy. The implantation inhibiting effect of the compound was assessed with respect to certain parameters which are characteristics of early pregnancy, such as tubal transport of ova into the uterus, hyperpermeability of the endometrial capillaries, increase in uterine weight and total protein content, endometrial bed preparation and changes in uterine phosphatase enzymes during Days 4-6 of pregnancy. The compound did not affect tubal transport of eggs, but the uterine blue reaction, caused by extravasation of the dye, pontamine blue, at future implantation sites was inhibited significantly in treated mice. Histological picture of the uterus revealed AA-induced impairment of development (i.e. decidualization) and reconciled with decreases found in uterine weight and its total protein contents in treated animals. In control untreated mice, specific uterine alkaline phosphatase (ALP) activity increased significantly from Days 4 through 6 of pregnancy, but this was prevented in treated mice. On the other hand, specific uterine acid phosphatase (AP) activity was high on Day 5, while in treated mice uterine AP activity remained low during Days 4 and 5 and increased significantly thereafter. It was inferred that AA interferes with steroidal conditioning of the uterus and renders it hostile to ovum implantation.

Sperm immobilizing effect of triterpene saponins from Acacia auriculiformis.

A mixture of two partially triterpenoid saponins (Tg), isolated from Acacia auriculiformis was tested for sperm immobilizing activity by using in vitro system. The lowest concentration (ED) required for an obvious immobilization of human sperm by using a modified Sander-Cramer test was found to be 0.35 mg/ml in physiological saline. The ability of the compound as a sperm immobilizing agent was compared with that of Triton X-100 and found to be more potent. Cervical mucus penetration test was also performed and the ED successfully prevented sperm entry in human cervical mucus. Supra-vital staining with eosin-nigrosin indicated death of the treated sperm. Electron microscopic study of Tg-treated sperm showed plasma membrane disintegration and dissolution of acrosomal cap which is presumably the cause for the spermicidal effect of the saponins. No permanent lesion was observed after application of 1.25 mg/ml Tg solution in physiological saline to the eye of rabbits for ten consecutive days.

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent: II. Possible mode of action with reference to anti-implantation effect of the benzene extract.

Benzene extractives of Hibiscus rosa-sinensis flowers, administered during day 1-4 of gestation, exerted anti-implantation effect without affecting the tubal transport of zygote. On day 4, normal number of blastocyst was present in the uterus but they did not implant. However, as studied by pontamine blue reaction, it was evident that hyper-permeability of the endometrial capillaries which is the earliest known response of a receptive endometrium to any kind of deciduogenic stimulus was inhibited by the extract. The magnitude of decidualization, as assessed by weight of the traumatized uterine horn and supported by the histological pictures of the uteri was significantly lower in comparison to that of the controls. Ovarian structure exhibited signs of luteolysis. Inadequate progestational development of the endometrium due to interference with the conditioning of the uterus with progesterone during prenidatory phase of pregnancy has been suggested as the plausible cause of the extract-induced implantation failure.

Effect of Malvaviscus conzattii flower extract on male fertility.

Chronic administration of Malvaviscus conzattii (MCV) flower extract at a dose level of 800 mg/kg b.w. for 30 consecutive days in male rats significantly reduced sperm counts and motility together with histological changes in testes. Mating with these treated animals three weeks following the drug schedule proved to be consistently infertile.

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent. III: Interceptive effect of benzene extract in mouse.

In mouse, oral administration of the benzene extract of Hibiscus rosa-sinensis flowers at a dose level of 1 gm/kg body weight/day from day 5-8 of gestation led to termination of pregnancy in about 92% of the animals. The effect was associated with a significant fall in peripheral level of progesterone and increase in uterine acid phosphatase activity, as measured on day 10. The ovary exhibited signs of luteolysis, and the corpus luteal delta 5-3 beta -hydroxysteroid dehydrogenase activity decreased markedly. The interceptive effect of the extract was prevented completely by exogenous progesterone (1 mg/mouse/day) or chorionic gonadotropin (1 I.U./mouse/day) and partially (62.5%) by exogenous prolactin (500 micrograms/mouse/day). In unilaterally pregnant mouse having trauma-induced deciduomata in the sterile horn, the extract caused resorption of the fetuses, and regression of the deciduomata accompanied by reduction in weight of the ovaries. Luteolysis, may be due to interference with the luteotropic influence, and a consequent fall in plasma level of progesterone have been suggested as the plausible cause of termination of pregnancy.

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent: I. effect of benzene extract on implantation of mouse.

In mouse, the benzene extract of Hibiscus rosa-senensis flowers was administered at four different dose levels (250-1000 mg/kg body weight/day) from day 1-4 postcoitus. Anti-implantation response and associated changes in the uterine chemical composition were studied. With an increase in the dosage of the extract, the percentage of implantation failure increased. At the dose level of 1 gm/kg body weight, the extract led to failure of implantation in 93% of the mice. The effect was accompanied by adversely altered uterine weight, its protein content and alkaline and acid phosphatase activity. In another experiment, influence of the extract on uterine uptake of progesterone was studied in bilaterally ovariectomized mice treated with or without estrogen. It exerted neither inhibitory nor stimulatory influence on uterine progesterone uptake in untreated castrated mice but the estrogen-induced increase in the uptake level was significantly inhibited by the extract. Failure of uterine bed preparation due to antiestrogenic potentiality of the extract has been discussed as the plausible cause of implantation failure.

The role of antioxidant activity of Phyllanthus emblica fruits on prevention from indomethacin induced gastric ulcer.

Pretreatment with the butanol extract of the water fraction of Phyllanthus emblica fruits at the dose of 100 mg/kg body-weight, orally administered to rats for 10 consecutive days, was found to enhance secretion of gastric mucus and hexosamine (P<0.001) in the indomethacin induced ulceration of rats. The morphological observations also supported a protective effect of the stomach wall from lesion. The indomethacin treatment of the premedicated animals with the drug hardly affected either the malondialdehyde (MDA) or superoxide dismutase (SOD) level in gastric tissue while the ulcerative agent itself significantly enhanced both the levels. An antioxidant property appears to be predominantly responsible for this cytoprotective action of the drug.

Abortifacient principle of Achyranthes aspera Linn.

PIP: Achyranthes apsera is an abundant indigenous herb in India. Extracts of the whole plant had shown an abortifacient effect in mice. Maximal activity was in the benzene extract which was tested. The drug, in olive oil, was given orally to rabbits in doses of 50 mg/kg of body weight on the 8th day postcoitum. Laparotomy was done on the 11th day. No implantation sites were found. However, ovaries contained prominent corpus luteum, indicating that the drug had prevented pregnancy. In rats, the drug was given orally as a single dose of 50 mg/kg of body weight on the 6th or 7th day after mating. No effect was observed. In mice the drug was given at a single dose of either 10, 15, 25, or 50 mg/kg of body weight. For toxicity tests in mice, a single dose of 1000 mg/kg of body weight was given. After 1 month animals were autopsied and the organs examined. The drug was nontoxic. For a chronic toxicity test 75 mg/kg of body weight was given every 21 days. After 6 months of drug treatment, blood and tissue samples were examined. No toxic effects were observed. For a teratogenic study, 15 mated female mice were fed 10 or 25 mg/kg of body weight on Day 6 of gestation. 3 generations of offspring showed no malformations. In mice, abortifacient effects were noted with a maximum activity at 50 mg/kg of body weight. The drug showed no estrogenic, antiestrogenic, or androgenic effects in mice. Progesterone or pituitary extract given along with the drug did not prevent abortions in mice. The drug was species-specific in that no abortifacient effect was found in rats.^ieng

A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat.

Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses.