A proposed role for VEGF isoforms in sex-specific vasculature development in the gonad.

Many scientists have expended efforts to determine what regulates development of an indifferent gonad into either a testis or ovary. Expression of Sry and upregulation of Sox9 are factors that initiate formation of the testis-specific pathway to allow for both sex-specific vasculature and seminiferous cord formation. Migration of mesonephric precursors of peritubular myoid cells and endothelial cells into the differentiating testis is a critical step in formation of both of these structures. Furthermore, these events appear to be initiated downstream from Sry expression. Sertoli cell secretion of growth factors acts to attract these mesonephric cells. One hypothesis is that a growth factor specific for these cell linages act in concert to coordinate migration of both peritubular and endothelial cells. A second hypothesis is that several growth factors stimulate migration and differentiation of mesonephric 'stem-like' cells to result in migration and differentiation into several different cell lineages. While the specific mechanism is unclear, several growth factors have been implicated in the initiation of mesonephric cell migration. This review will focus on the proposed mechanisms of a growth factor, Vascular Endothelial Growth Factor, and how different angiogenic and inhibitory isoforms from this single gene may aid in development of testis-specific vascular development.

Frequency of luteinizing hormone pulses in cattle influences duration of persistence of dominant ovarian follicles, follicular fluid concentrations of steroids, and activity of insulin-like growth factor binding proteins.

The objectives of the present study were to determine how varying frequency of LH pulses as controlled by varying treatments with progesterone (P4) in cattle would affect: (1) concentration of steroid hormones and activity of insulin-like growth factor binding proteins (IGFBPs) in the ovarian follicular fluid and blood plasma, and (2) duration of persistence of largest ovarian follicles. There were four treatment groups (n=7 per group) and a control group (n=5) of mature, non-lactating beef cows. Treatments were: (1) two progesterone releasing intravaginal devices (PRIDs) for 16 days (2PRID); (2) a half PRID for 16 days (0.5PRID); (3) two PRIDs for 8 days, then a half PRID for 8 days (2-0.5PRID); or (4) a half PRID for 8 days, then two PRIDs for 8 days (0.5-2PRID). Treatment was initiated on the fifth day of the estrous cycle, which was designated as Day 0, and continued for 16 days. All P4-treated females were administered prostaglandin F2alpha on Day 0 and 1 to regress their corpora lutea. Frequency of LH pulses was greater during treatment with the smaller dose of P4 compared with treatment with the larger dose of P4 and the control group. Ovarian follicles were classified into five categories based on ultrasonographic observations: growing (G); atretic (A); growing dominant (GD); growing persistent (GP); or atretic persistent (AP). At ovariectomy on Day 16, the largest and second largest follicles collected were re-classified into five categories based on follicular concentration of steroids. Classification of the largest follicle collected on Day 16 was influenced by treatment (P<0.005), with the 2PRID group having A follicles, the 2-0.5PRID group GP follicles, the 0.5-2PRID group AP follicles, and the 0.5PRID group GD and GP follicles. Concentrations of 17beta-estradiol (E2) were greatest in GD and GP follicles (P<0.05). There was less (P<0.05) activity of IGFBP-2 in GD follicles and less (P<0.05) activity of IGFBP-3 in GD and GP follicles than other follicles. Activity of IGFBP-4 and -5 was greater (P<0.05) in A and AP follicles than G, GD, and GP follicles. Maintenance of a frequent release of LH pulses over a 16-day period did not result in maintenance of persistent follicles throughout this period indicating that duration of dominance of these follicles is finite even when there is frequent release of LH pulses. Follicular atresia is associated with greater activity of IGFBP-2, -4, -5, and greater concentrations of P4 in follicles, whereas growing dominant and persistent follicles contained greater concentrations of E2, androstenedione (A4), and less IGFBP-2 activity than follicles of other classes. Follicle classifications based on ultrasonography or follicular concentration of steroids did differ (P<0.05) for the largest follicles from the 2PRID group. Two follicles in this group appeared as GD follicles by ultrasonography, but these were atretic based on follicular steroid contents. Objective 1 of the present study yielded the conclusion that concentrations of steroid hormones in follicular fluid and blood plasma could be predictably controlled by regulating the frequency of LH pulses with varying doses of P4. Objective 2 yielded the conclusion that maintain frequent release of LH pulses over a 16-day period could not maintain persistent follicles throughout this period, indicating that duration of dominance of these follicles is finite even when there is frequent release of LH pulses. Follicular atresia in the present study was associated with increased follicular fluid activity of IGFBP-2, -4, -5, and P4, whereas growing dominant and persistent follicles contained greater concentrations of E2, A4, and less IGFBP-2 activity than follicles of other classes.

Recent advances in bovine reproductive endocrinology and physiology and their impact on drug delivery system design for the control of the estrous cycle in cattle.

When methods of drug intervention are being developed to control estrous cycles, a thorough understanding of the endocrine and functional changes together with the reproductive behavior of the animals are essential. This review presents our current knowledge on reproductive endocrinology, physiology and behavior, and the methods of drug intervention to control estrous cycles. It also describes current efforts to develop advanced drug delivery systems that meet the animal scientist's demands to control the estrous cycle in cattle.

Corpus luteum development and function in cattle with episodic release of luteinizing hormone pulses inhibited in the follicular and early luteal phases of the estrous cycle.

The influence of episodic LH pulses before and subsequent to ovulation on size and function of the corpus luteum (CL) in cattle was examined. Treatments were 1) control; 2) LHRH antagonist starting 2 days before the preovulatory LH surge (Antagonist [Ant] -2); 3) LHRH antagonist at initiation of the preovulatory LH surge (Ant 0); and 4) LHRH antagonist starting 2 days after the preovulatory LH surge (Ant 2). Treatments with an LHRH antagonist were continued until 7 days after the preovulatory surge. Diameter of the CL and concentrations of progesterone were monitored during the luteal phase that ensued after treatment. Maximum average diameters of CL were 9.5, 17.5, 21.6, and 28.8 mm for females from the Ant -2, Ant 0, Ant 2, and control groups, respectively (P < 0. 01). Compared with those in control animals, concentrations of progesterone in plasma were less (P < 0.01) in animals in which release of LH pulses was inhibited by treatment with antagonist. Arbitrary units under the curve for concentrations of progesterone during the luteal phase of the estrous cycle for Ant -2, Ant 0, Ant 2, and control groups were 19.6, 41.6, 43.6, and 142.2, respectively. There was no difference in circulating concentrations of progesterone (P > 0.1) among antagonist-treated groups. In conclusion, episodic release of LH pulses before, during, and after the time of the preovulatory surge of LH may stimulate development and function of the CL in cattle.

Copper-specific damage in human erythrocytes exposed to oxidative stress.

Ascorbate and complexes of Cu(II) and Fe(III) are capable of generating significant levels of oxygen free radicals. Exposure of erythrocytes to such oxidative stress leads to increased levels of methemoglobin and extensive changes in cell morphology. Cu(II) per mole is much more effective than Fe(III). However, isolated hemoglobin is oxidized more rapidly and completely by Fe(III)- than by Cu(II)-complexes. Both Fe(III) and Cu(II) are capable of inhibiting a number of the key enzymes of erythrocyte metabolism. The mechanism for the enhanced activity of Cu(II) has not been previously established. Using intact erythrocytes and hemolysates we demonstrate that Cu(II)-, but not Fe(III)-complexes in the presence of ascorbate block NADH-methemoglobin reductase. Complexes of Cu(II) alone are not inhibitory. The relative inability of Fe(III)-complexes and ascorbate to cause methemoglobin accumulation is not owing to Fe(III) association with the membrane, or its failure to enter the erythrocytes. The toxicity of Cu(II) and ascorbate appears to be a result of site-specific oxidative damage of erythrocyte NADH-methemoglobin reductase and the enzyme's subsequent inability to reduce the oxidized hemoglobin.

Low-level oxidative stress causes cell-cycle specific arrest in cultured cells.

Oxidative stress is involved in a multitude of pathological conditions. In the present study, cell cycle arrest was demonstrated in monolayer cultures of Chinese hamster ovary cells subjected to low-level oxidative stress induced by the addition of hydrogen peroxide. Fluorescence-activated cell sorting analysis characterized this arrest as occurring in both the G1 and G2/M phases of the cell cycle. Upon exposure to oxidative stress, cells in G1 arrest in G1, while S-phase cells complete DNA synthesis and subsequently arrest in G2/M. Nitroxide spin labels with differing permeabilities are able to protect the cells, which suggests that both the G1 and the G2/M arrest involve oxidation of targets located at the cell surface.

Sites and mechanisms of low-level oxidative stress in cultured cells.

Oxidative stress is involved in a multitude of pathological conditions. In the present study, we investigated the cellular targets and the mechanisms of low-level oxidative stress in a Chinese Hamster Ovary cell culture. Oxidative stress was induced either by continuous enzymatic production of superoxide or by bolus addition of hydrogen peroxide (H2O2). Low-level oxidative stress irreversibly impaired the reproductive capacity of the cells in the absence of damage to membrane integrity or energy metabolism. Cells were protected by catalase but not by superoxide dismutase, indicating that H2O2, not superoxide, was the causative agent of cell damage. Nitroxide spin labels decreased hydroxyl radical (.OH) formation and protected cells from the oxidative stress. The differing membrane permeabilities of these spin labels suggest that the damage is localized on the cell surface. Oxidative stress to DNA and RNA was not significant, as shown by levels of guanine hydroxylation products. A mechanism is proposed whereby low-level oxidative stress acts at the cell surface to cause impairment of cell reproduction.

Access to postpartum sterilization in southeast Brazil.

All women hospitalized for delivery over a ten-week period at the largest maternity hospital in Campinas in the State of São Paulo, Brazil, were questioned about their interest in and plans for sterilization. Results from a categorical data analysis indicate that among the study variables, cesarean delivery was the necessary condition for postpartum sterilization and was significantly associated with the patient's ability to pay for services. Further, the variability in the proportion of women sterilized postpartum was almost perfectly explained by a linear model with main effects for parity and for the patient's ability to pay for services.

PIP: A study was undertaken at a large maternity hospital in Campinas in the State of Sao Paulo, Brazil in an effort to obtain more information concerning access to sterilization. This hospital was chosen because it serves patients of widely varied socioeconomic status, and, consequently of different abilities to pay for surgery. The study was conducted over the December 1979 through February 1980 period. Interviews were completed with 2194 women after they gave birth and before discharge from the hospital. Analysis proceeds in 3 steps: a description concerning distributions of age, parity (after delivery), monthly family income, type of payment for medical services, and method of delivery among the 927 women who desire no more children; a description of how the population desiring no more children chooses sterilization as the preferred family planning method; and focus on the subset of women preferring sterilization services, making use of methods of estimation and hypothesis testing from cross-classified data. Almost 9 of 10 women who want no more children have heard of sterilization. Indigent patients are least likely (79%) and private patients are most likely (98%) to have heard of sterilization. Women who had cesarean deliveries are more likely to have heard of sterilization (95%) than those giving birth vaginally (86%). Of all women who want no more children and have heard of sterilization, 58% stated that they had planned to be sterilized. Of the 375 women who planned to be sterilized and knew about available services, 40% were not sterilized postpartum. The most frequent reason given was type of delivery (38%). Of the women who had vaginal deliveries, 48% gave this as a reason for failure to be sterilized. Study data show that the method of payment for care substantially influences the eventuality of sterilization. Wealthier women who are private or convenio (all women who pay for their care through a privately financed insurance plan but do not stay in a private room) patients are more likely to be sterilized than are the poor, whose care is financed through government insurance or who are indigent. Results also show that women sterilized postpartum almost always have had cesarean deliveries. Regardless of whether she is sterilized, a cesarean delivery is more likely as the socioeconomic status of the woman rises. A more liberal interpretation of the Medical Ethics Code that would consider women to be at high risk for reasons other than those associated with previous cesarean birth would improve access to postpartum sterilization.

Epidemiology of Ocular Allergy in Trinidad & Tobago

Ocular allergy (OA) is also known as hypersensitivity disorder to normally harmless substances, or an allergic reaction of the eye's surface to allergens in the environment. Globally it is highly prevalent and is non-discriminatory amongst age groups. It might be asymptomatic or produce significant symptoms, including visual loss in extreme cases. Universally, it has varying manifestations and associating factors which makes it difficult to apply any informational studies in practice, leading to its misdiagnosis and undertreatment. For a disorder that is on a global rise in prevalence, it is alarming that there is little to no research on OA in Trinidad and Tobago, and is yet to be studied in the Caribbean region (AU)