Aetiology and pathogenesis of endometriosis - a review.

Endometriosis is a complex gynaecological disorder that affects nearly 1 in 7 women of reproductive age. Ectopic dissemination of endometrial cell and their subsequent implantation are the mechanisms involved in the development of endometriosis. Endometriosis is a common multifactorial disease caused by an interaction between multiple gene loci and environment. Causes of stress on immune functioning or may be genetically determined. Environmental factors can be responsible for immunosuppressive activities in patient with endometriosis. In addition, toxin modulates steroid receptors expression resulting in altered tissue specific responses to hormones. Chronic immunosuppression in combination with hormonal regulation may have facilitated the aberrant growth of endometrial tissue within the peritoneum. However, the mechanism appears to require endometrium and retrograde menstruation in most cases of the disease.

Effect of supplementation of dermal fibroblasts conditioned medium on expansion of keratinocytes through enhancing attachment.

In the present study in vitro expansion of human keratinocytes by supplementing dermal fibroblasts conditioned medium (DFCM) has been reported. Effect of two different DFCM acquired by culturing fibroblasts in keratinocyte-specific medium (defined keratinocytes serum free medium, DFCM-DKSFM) and fibroblast-specific serum free medium (F12: DMEM nutrient mix, DFCM-FD) have been compared. Growth kinetics of keratinocytes in terms of efficiency of cell attachment, expansion index, apparent specific growth rate and growth potential at the end of culture was evaluated in culture supplemented with DFCM-DKSFM and DFCM-FD in comparison with control i.e. DKSFM only. Results indicated that supplementation of DFCM caused significant increase in keratinocyte attachment. Efficiency of keratinocyte attachment in culture supplemented with bFCM-DKSFM was significantly higher compared to those cultured in DFCM-FD and DKSFM. In addition, the expansion index of keratinocytes in cultures supplemented with DFCM-DKSFM and DFCM-FD were 3.7 and 2.2 times higher than that of control condition even though the apparent growth rate and proliferative potential was found significantly lower. These results suggested that supplementation of DFCM enhanced expansion of keratinocyte by increasing efficiency of cell attachment, and DFCM-DKSFM provided suitable condition for in vitro expansion of keratinocytes compared to DFCM-FD and control condition.

Composition analysis and material characterization of an emulsifying extracellular polysaccharide (EPS) produced by Bacillus megaterium RB-05: a hydrodynamic sediment-attached isolate of freshwater origin.

AIMS: This work was aimed to isolate, purify and characterize an extracellular polysaccharide (EPS) produced by a freshwater dynamic sediment-attached micro-organism, Bacillus megaterium RB-05, and study its emulsifying potential in different hydrocarbon media. METHODS AND RESULTS: Bacillus megaterium RB-05 was found to produce EPSs in glucose mineral salts medium, and maximum yield (0.864 g l(-1) ) was achieved after 24-h incubation. The recovery rates of the polysaccharide material by ion-exchange and gel filtration chromatography were around 67 and 93%, respectively. As evident from HPLC and FT-IR analyses, the polysaccharide was found to be a heteropolymer-containing glucose, galactose, mannose, arabinose, fucose and N-acetyl glucosamine. Different oligosaccharide combinations namely hexose(3), hexose(4), hexose(5) deoxyhexose(1) and hexose(5) deoxyhexose(1) pentose(3) were obtained after partial hydrolysis of the polymer using MALDI-ToF-MS. The polysaccharide with an average molecular weight of 170 kDa and thermal stability up to 180°C showed pseudoplastic rheology and significant emulsifying activity in hydrocarbon media. CONCLUSIONS: Isolated polysaccharide was found to be of high molecular weight and thermally stable. The purified EPS fraction was composed of hexose, pentose and deoxyhexose sugar residues, which is a rare combination for bacterial polysaccharides. Emulsifying property was either better or comparable to that of other commercially available natural gums and polysaccharides. SIGNIFICANCE AND IMPACT OF THE STUDY: This is probably one of the few reports about characterizing an emulsifying EPS produced by a freshwater sediment-attached bacterium. The results of this study contribute to understand the influence of chemical composition and material properties of a new microbial polysaccharide on its application in industrial biotechnology. Furthermore, this work reconfirms freshwater dynamic sediment as a potential habitat for bioprospecting extracellular polymer-producing bacteria. This study will improve our knowledge on the exploitation of a nonconventional renewable resource, which also seems to be ecologically significant.

Synergistic Effect of Laminin and Epidermal Growth Factor on Biological and Morphological Properties of Co-Cultured Myoblasts and Fibroblasts.

BACKGROUND: One of the long-standing problems of myoblasts in vitro expansion is slow cell migration and this causes fibroblast population to exceed myoblasts. In this study, we investigated the synergistic effect of laminin and epidermal growth factor (EGF) on co-cultured myoblasts and fibroblasts for cell attachment, proliferation and migration. METHODS: Skeletal human muscle cells were cultured in four different conditions; control, EGF, laminin (Lam) and laminin EGF (Lam + EGF). Using live imaging system, their cellular properties; attachment, migration and growth were exposed to Rho kinase inhibitor, Y-27632, and EGF-receptor (EGF-R) inhibitor, gefitinib were measured. RESULTS: Myoblast migration and proliferation was enhanced significantly by synergistic stimulation of laminin and EGF (0.61 ± 0.14 µm/min, 0.008 ± 0.001 h-1) compare to that by EGF alone (0.26 ± 0.13 µm/min, 0.004 ± 0.0009 h-1). However, no changes in proliferation and migration were observed for fibroblasts among the culture conditions. Inhibition of Rho kinase resulted in the increase of the myoblast migration on the laminin-coated surface with EGF condition (0.64 ± 0.18 µm/min). Compared to the untreated conditions, myoblasts cultured on the laminin-coated surface and EGF demonstrated elongated morphology, and average cell length increase significantly. In contrast, inhibition of EGF-R resulted in the decrease of myoblast migration on the laminin coated surface with EGF supplemented condition (0.43 ± 0.05 µm/min) in comparison to the untreated control (0.53 ± 0.05 µm/min). CONCLUSION: Laminin and EGF preferentially enhance the proliferation and migration of myoblasts, and Rho kinase and EGF-R play a role in this synergistic effect. These results will be beneficial for the propagation of skeletal muscle cells for clinical applications.

Preconception care of women attending adult general diabetes clinics--are we doing enough?

BACKGROUND: The presence of diabetes in pregnancy can result in substantial morbidity to both mother and baby if management is sub-optimal. AIMS: To assess the process of standards of preconception care (against the National Service Framework standards) of women attending the adult general diabetes clinics in a district general hospital. METHODS: Retrospective review of case notes of women aged 18-40 years attending the general diabetes clinics for annual review, over a period of 6 months. RESULTS: Seventy sets of notes were reviewed. The mean age of the patients was 32 years. Fifty-six patients had type-1 diabetes and 14 patients had type-2 diabetes. Mean duration of diabetes was 13 years. Eighty-six percent of the patients had blood pressure recordings documented. Mean blood pressure was 124/74 mmHg. Mean HbA1c was 9.1%. Documented evidence of home blood glucose monitoring was seen in 66% of the patients. Preconception counselling/contraception were discussed in 17 patients (25%). Twenty-nine patients (41%) were on potentially teratogenic medications. Alcohol and smoking history was not documented in 91% and 61% of the patients, respectively. CONCLUSIONS: This retrospective assessment highlights that reproductive issues in an at risk population of women with diabetes are not included in routine management of diabetes care in outpatient clinics.

Effects of feeding grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of laying hens, turkey poults, and broiler breeder hens.

Three experiments were conducted to compare the effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of laying hens, turkey poults, and broiler breeder hens. In Experiment 1, thirty-six 45-wk-old laying hens were fed diets including the following for 4 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent (GMA). Concentrations of brain neurotransmitters and metabolites were analyzed in pons, hypothalamus, and cortex by HPLC with electrochemical detection. Neurotransmitters and the metabolites measured included dopamine, 3,4-dihydroxylphenyacetic acid, homovanillic acid, serotonin [5-hydroxytryptamine (5-HT)], 5-hydroxyindolacetic acid, epinephrine, and norepinephrine. The feeding of contaminated grains significantly increased concentrations of 5-HT and decreased the 5-hydroxyindolacetic acid:5-HT in the pons region in the brain stem. Dietary supplementation with GMA prevented these effects. There was no effect of diet on concentrations of other neurotransmitters or metabolites in the pons, hypothalamus, or cortex. In Experiment 2, thirty-six 1-d-old turkey poults were fed diets including the following for 4 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% GMA. Hypothalamic, pons, and cortex neurotransmitter concentrations were not affected by diet. In Experiment 3, forty-two 26-wk-old broiler breeder hens were fed diets including the following for 15 wk: 1) control, 2) contaminated grains, and 3) contaminated grains + 0.2% GMA. There was no effect of diet on neurotransmitter concentrations in the pons, hypothalamus, or cortex. It was concluded that differences in intraspecies effects of these mycotoxins on brain neurotransmitter concentrations might explain the intraspecies differences in the severity of Fusarium mycotoxin-induced reductions in feed intake.

Ovine tendon collagen: Extraction, characterisation and fabrication of thin films for tissue engineering applications.

Collagen is the most abundant extracellular matrix (ECM) protein in the human body, thus widely used in tissue engineering and subsequent clinical applications. This study aimed to extract collagen from ovine (Ovis aries) Achilles tendon (OTC), and to evaluate its physicochemical properties and its potential to fabricate thin film with collagen fibrils in a random or aligned orientation. Acid-solubilized protein was extracted from ovine Achilles tendon using 0.35M acetic acid, and 80% of extracted protein was measured as collagen. SDS-PAGE and mass spectrometry analysis revealed the presence of alpha 1 and alpha 2 chain of collagen type I (col I). Further analysis with Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) confirms the presence of triple helix structure of col I, similar to commercially available rat tail col I. Drying the OTC solution at 37°C resulted in formation of a thin film with randomly orientated collagen fibrils (random collagen film; RCF). Introduction of unidirectional mechanical intervention using a platform rocker prior to drying facilitated the fabrication of a film with aligned orientation of collagen fibril (aligned collagen film; ACF). It was shown that both RCF and ACF significantly enhanced human dermal fibroblast (HDF) attachment and proliferation than that on plastic surface. Moreover, cells were distributed randomly on RCF, but aligned with the direction of mechanical intervention on ACF. In conclusion, ovine tendon could be an alternative source of col I to fabricate scaffold for tissue engineering applications.

Effects of feeding grains naturally contaminated with Fusarium mycotoxins on hepatic fractional protein synthesis rates of laying hens and the efficacy of a polymeric glucomannan mycotoxin adsorbent.

Experiments were conducted to evaluate the effects of feeding grains naturally contaminated with a combination of Fusarium mycotoxins on hepatic fractional protein synthesis rates (FSR) of laying hens. Thirty-six 32-wk-old laying hens were fed diets formulated with 1) uncontaminated grains, 2) contaminated grains, or 3) contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent for a period of 4 wk. Hepatic FSR were measured in vivo by the flooding-dose method. The feeding of contaminated grains decreased hepatic FSR in laying hens compared with controls after 4 wk. The hepatic FSR of birds fed contaminated grains and contaminated grains + glucomannan mycotoxin adsorbent were not different. It was concluded that the in vivo hepatic FSR of laying hens was inhibited by the feeding of grains naturally contaminated with Fusarium mycotoxins and that this may explain some of the adverse effects seen when contaminated grains were fed to laying hens.

Effects of feed-borne Fusarium mycotoxins on hematology and immunology of turkeys.

Feeding grains naturally-contaminated with Fusarium mycotoxins has been shown to alter the metabolism and performance of turkeys. The objectives of the current experiment were to examine the effects of feeding turkeys with grains naturally contaminated with Fusarium mycotoxins on their hematology and immunological indices (including functions), and the possible protective effect of feeding a polymeric glucomannan mycotoxin adsorbent (GMA). Two hundred twenty-five 1-d-old male turkey poults were fed corn, wheat, and soybean meal-based starter (0 to 3 wk), grower (4 to 6 wk), developer (7 to 9 wk), and finisher (10 to 12 wk) diets formulated with uncontaminated grains, contaminated grains, or contaminated grains with 0.2% GMA. The chronic consumption of Fusarium mycotoxins caused minor and transient changes in hematocrit (0.33 L/L) and hemoglobin (10(6) g/L) concentrations as well as in blood basophil (0.13 x 10(9)/L) and monocyte counts (3.42 x 10(9)/L) compared with controls. Supplementation of the contaminated diet with GMA prevented these effects on blood cell counts. Biliary IgA concentrations were significantly increased (4.45-fold) when birds were fed contaminated grains compared with controls, but serum IgA concentrations were not affected. Contact hypersensitivity to dinitrochlorobenzene, which is a CD8+ T-cell-mediated delayed-type hypersensitivity response, was decreased (48%) by feed-borne mycotoxins compared with the control. By contrast, the primary and secondary antibody response to sheep red blood cells, a CD4+ T-cell-mediated response, was not affected. It was concluded that chronic consumption of grains naturally contaminated with Fusarium mycotoxins exerts only minor adverse effects on the hematology and some immunological indices of turkeys. Consumption of grains naturally contaminated with Fusarium mycotoxins may, however, increase the susceptibility of turkeys to infectious agents against which CD8+ T cells play a major role in defense.

Effects of feed-borne Fusarium mycotoxins on hematology and immunology of laying hens.

Feeding grains naturally contaminated with Fusarium mycotoxins has been shown to alter metabolism and performance of laying hens. The objectives of the current experiment were to examine the effects of feeding grains naturally contaminated with Fusarium mycotoxins on hematology and immunological indices and functions of laying hens and the possible protective effect of feeding a polymeric glucomannan mycotoxin adsorbent (GMA). One hundred forty-four laying hens were fed for 12 wk with diets formulated with (1) uncontaminated grains, (2) contaminated grains, or (3) contaminated grains + 0.2% GMA. Fusarium mycotoxins such as deoxynivalenol (DON, 12 mg/kg), 15-acetyl-DON (0.5 mg/kg), and zearalenone (0.6 mg/kg) were identified in the contaminated diets arising from contaminated grains grown in Ontario, Canada. The concentrations of DON arising from naturally contaminated grains in this study were similar to purified mycotoxin fed to experimental mice. The chronic feeding of Fusarium mycotoxins induced small decreases in hematocrit values, total numbers of white blood cells, lymphocytes including both CD4+ and CD8+ T lymphocytes and B lymphocytes, and biliary IgA concentration. Supplementation of diets containing feedborne mycotoxins with GMA prevented the reduction in total number of B lymphocytes in the peripheral blood and the reduction in biliary IgA concentration. In addition, the delayed-type hypersensitivity response to dinitrochlorobenzene was increased by feed-borne mycotoxins, whereas IgG and IgM antibody titers to sheep red blood cells were not affected by diet. We concluded that chronic consumption of grains naturally contaminated with Fusarium mycotoxins at levels likely to be encountered in practice were not systemically immunosuppressive or hematotoxic; however, mucosal immunocompetence needs to be explored further.

Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immunocompetence of ducklings.

Experiments were conducted to determine the effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immune competence of ducklings. Four hundred sixty-four 1-d-old White Pekin male ducklings were fed starter (0 to 2 wk), grower (3 to 4 wk), and finisher (5 to 6 wk) diets formulated with uncontaminated grains, a low level of contaminated grains, a high level of contaminated grains, or the higher level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent. Body weight gains, feed consumption, and feed efficiency were not affected by diet. However, consumption of contaminated grains decreased plasma calcium concentrations after 2 wk and plasma uric acid concentrations at the 4-wk assessment point. Mean corpuscular hemoglobin concentrations and hematocrit decreased when ducks were fed contaminated grains for 4 or 6 wk, respectively. In contrast, total numbers of white blood cells and lymphocytes increased transiently in birds fed contaminated grains for 4 wk. The antibody response to sheep red blood cells (CD4+ T cell dependent) and the cell-mediated response to phytohemagglutinin-P (also CD4+ T cell dependent) were not affected by diet, but consumption of contaminated grains for 6 wk decreased the duration of peak cell-mediated response to dinitrochlorobenzene (CD8+ T cell dependent) assessed in a skin test. Feeding grains naturally contaminated with Fusarium mycotoxins, even at levels widely regarded as high, exerted only minor adverse effects on plasma chemistry and hematology of ducklings, and production parameters were unaffected in this avian species. Mycotoxin-contaminated feeds may, however, render these animals susceptible to infectious agents such as viruses against which the CD8+ T cell provides necessary defence. Glucomannan mycotoxin adsorbent was not effective in preventing alterations caused by Fusarium mycotoxins.

Effects of dietary tamarind on cholesterol metabolism in laying hens.

An experiment was conducted to evaluate the potential for dietary tamarind to alter serum and egg yolk cholesterol concentrations and overall performance in different layer strains. Thirty, 43-wk-old, Hisex Brown, ISA Brown, Lohmann Brown, Starcross Brown, Babcock B-300, and Starcross-579 strains (5 hens per strain) were fed diets supplemented with 0 (control), 2, 4, 6, or 8% oven-dried tamarind for 6 wk. Egg production, egg mass, and efficiency of feed utilization followed a quadratic response with a maximum when the diet contained 2% tamarind and a minimum when 8% tamarind was fed (P < 0.05). There were no differences (P > 0.05) among strains for egg production, egg weight, yolk weight, egg mass, feed consumption, or feed efficiency. Yolk weight increased linearly (P < 0.05) with increasing levels of dietary tamarind in wk 1, 2, and 3 as well as when averaged over 6 wk. Egg yolk cholesterol concentrations were not affected by dietary tamarind. Serum cholesterol concentrations, however, decreased quadratically with increasing levels of dietary tamarind (P < 0.05). It was concluded that 2% supplemental dietary tamarind could decrease serum cholesterol concentrations and increase layer performance.

Surface modification of electrospun poly(methyl methacrylate) (PMMA) nanofibers for the development of in vitro respiratory epithelium model.

Scaffold design is an important aspect of in vitro model development. In this study, nanoscaffold surface modification, namely UV radiation and genipin cross-linking to immobilize collagen on the surface of electrospun poly (methyl methacrylate) (PMMA) nanofiber sheet was investigated. Samples were divided into four groups; PMMA nanofibers (PMMA), collagen-coated PMMA nanofibers (PMMACOL), genipin cross-linked collagen-coated PMMA nanofibers (PMMAGEN), and UV-irradiated collagen-coated PMMA nanofibers (PMMAUV). 6 h of UV radiation significantly reduced the hydrophobicity of PMMA nanofibers from (131.88° ± 1.33°) to (110.04° ± 0.27°) (p < 0.05). The amount of collagen immobilized was significantly higher in PMMAGEN group (239.36 ± 16.63 µg collagen/mg nanofibers) (p < 0.05) compared to the other groups. RECs on all scaffold expressed epithelial cell-specific markers (CK18 and CK14), mucin-producing cell marker (MUC5Ac) and were actively proliferating, based on the positive expression of Ki67. Total number of attached cells was significantly the highest in PMMAUV group on day 9 (6.44 × 10(4) ± 2.77 × 10(4) cells/cm(2)) and it has the highest proliferation rate from day 4 to 9 (0.005 ± 0.003 h(-1)) compared to the other groups. Even though PMMAGEN group showed the highest collagen adsorption, in terms of cells attachment and proliferation, PMMAUV group showed a better outcome compared to the other groups. Thus, PMMAUV scaffold is more suitable to be used in the construction of in vitro respiratory epithelial model.

Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.

PURPOSE: To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. METHODS: RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. RESULTS: No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. CONCLUSIONS: Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.

Uterine estradiol and progesterone receptor concentration in relation to circulating hormone levels and histoarchitecture during high endometrial sensitivity and induced decidualization in guinea pigs.

Alterations in nuclear and cytosolic estradiol (ER) and progesterone (PR) receptor concentration in the antimesometrial (AM) and mesometrial (M) segments of the uterus in relation to circulating hormone levels, histology and surface topography during the period of high endometrial sensitivity and development of trauma-induced decidualization in cyclic guinea pigs were investigated. The period of high endometrial sensitivity (i.e. day 5 of the estrous cycle) was characterized by elevated plasma estradiol and progesterone and their receptors in the nuclear and cytosolic fractions of the uterus. There was, however, no difference in the concentration of these receptors or the surface ultrastructure in the AM and M segments. Unilateral traumatization by scissor cut along the AM length of the uterus on day 5 of the estrous cycle induced decidual cell reaction resulting in a marked increase in weight of the decidualized (traumatized) uterine horn with advancing decidualization to reach maximum levels (926% of the contralateral nontraumatized uterine horn) 7 days after traumatization. This was associated with decidual transformation and a marked increase in nuclear and cytosolic ER and PR concentration in the AM segment of the traumatized uterine horn. An increase in receptor concentration in the M segment of the traumatized uterine horn or the AM segment of the nontraumatized uterine horn was transitory and of a low order. Receptor concentration in the M segment of the nontraumatized uterine horn remained low throughout days 8-12 of the cycle. Findings indicate a possible role of both estradiol and progesterone in induction of endometrial sensitivity and development and maintenance of decidua in the guinea pig.

Uterine estradiol and progesterone receptor concentration, activities of certain antioxidant enzymes and dehydrogenases and histoarchitecture in relation to time of secretion of nidatory estrogen and high endometrial sensitivity in rat.

Alterations in uterine nuclear and cytosolic estradiol (ER) and progesterone (PR) receptor concentration, activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH), surface and transmission electron microscopy and histology in relation to the time of secretion of nidatory estrogen and the onset of endometrial sensitivity in the rat were investigated. A significant increase in plasma estradiol (E2) concentration in control rats was observed at 22.00 h on day 4 post-coitum, whereas progesterone (P) concentration increased at 17.00 h on day 4 and was maintained until 17.00 h on day 5. The period of high endometrial sensitivity (10.00 h on day 5) was characterized by elevated uterine cytosolic ER and nuclear and cytosolic PR concentration and POD activity, low columnar luminal epithelium with undulating surface and intercellular membranes, covered with short microvilli and pinopods, and containing numerous electron-transparent apical vesicles, mitochondria, polyribosomes, rough (RER) and smooth (SER) endoplasmic reticulum, well developed Golgi, few lysosomes and lipid droplets and loose edematous antimesometrial stroma. Inhibition in endometrial sensitivity by post-coital centchroman was associated with a marked depletion in uterine cytosolic ER and an increase in nuclear ER concentration, a decrease in POD and G-6-PDH activities, compact fibroblastic stroma, an increase in luminal epithelial cell height with decreased RER, SER, polyribosomes, Golgi, straightening of intercellular membranes, reduced surface undulations and absence of pinopods. Electron-transparent vesicles appeared flattened and clumped in the apical portion of cells, tight junctions were more prominent and lipid droplets were translucent. Nuclear and cytosolic PR and the pattern of secretion or plasma E2 and P remained unaffected. CAT, SOD and LDH activities, although high throughout pre-implantation, did not vary in relation to the secretion of nidatory estrogen, endometrial sensitivity or centchroman treatment.

A primate model of anxiety.

Pentylenetetrazol (PTZ; 30 mg/kg, i.m.) produced an acute anxiogenic effect on the behaviour of a social colony of rhesus monkeys acclimatized to laboratory conditions. The animals exhibited hypervigilance, aggressiveness, tachypnea, piloerection and frequent change of posture and also had raised plasma cortisol levels. These effects of PTZ were antagonized by benzodiazepines (diazepam; 1 mg/kg, i.v. and alprazolam; 0.05 mg/kg, p.o.). Non-benzodiazepine anxiolytic drug (buspirone; 10 mg/kg, p.o.) blocked the behavioural effects but not the rise in plasma cortisol concentration. On the other hand, pretreatment with hypnosedative (promethazine; 5 mg/kg, i.m.) or anticonvulsant (sodium valproate; 40 mg/kg, p.o.) agents did not attenuate the effects of PTZ indicating the specificity of its anxiogenic response. The model, thus, seems suitable for evaluation of potential anxiolytic agents.

Early abortifacient action of RU 486 by continuous intravenous infusion in rat.

RU 486 administered through constant intravenous infusion at 20 mg/kg dose on day 8 of pregnancy induced frank vaginal bleeding and resorption of all implantations in 100% rats. This was associated with an almost 4-fold reduction in progesterone secretion rate by the dispersed luteal cells ex-vivo. At 12 mg/kg dose, an incomplete resorption of implantations was observed in all treated animals. Results indicate that slow and continuous intravenous infusion of this antiprogestin was highly effective in terminating pregnancy shortly after implantation in the rat and this could, at least partially, be related to its luteolytic action in this species.