The yin and yang of GSM and low sexual desire.

Numerous surveys have documented that sexuality and/or sexual activity is important to women at all stages of adulthood, including postmenopause. Genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD) are common disorders in postmenopausal women and may co-occur. Both are often undiagnosed due to a lack of knowledge of the disorder, health-care professional discomfort in discussing sexual problems or a lack of routine screening. It is incumbent upon health-care professionals to identify and differentiate these conditions in women through a biopsychosocial assessment, and may require a focused physical examination. Numerous treatments, both non-pharmacologic and pharmacologic, are available to address GSM and HSDD.

Guide RNA requirement for editing-site-specific endonucleolytic cleavage of preedited mRNA by mitochondrial ribonucleoprotein particles in Trypanosoma brucei.

RNA editing in trypanosome mitochondria entails the posttranscriptional internal addition and occasional deletion of uridines from precursor mRNAs. Ample evidence exists to show that the information specifying the site and number of uridines added or deleted comes from small, mitochondrially encoded guide RNAs (gRNAs). More recent work indicates that the process involves an enzymatic cascade, initiating with an endonucleolytic cleavage of the pre-mRNA at an editing site. The cleaved editing site can undergo uridine (U) addition to or deletion from the 3' end of the 5' fragment via a mitochondrial terminal uridylyl transferase (TUTase) or terminal uridylyl exonuclease, respectively. Mitochondrial RNA ligase subsequently rejoins the mRNA. Activities to carry out these processes have been found in trypanosome mitochondria, including an editing-site-specific endonuclease activity which cleaves preedited but not edited mRNAs. We have found that this enzymatic activity cosediments with the same 19S ribonucleoprotein particle previously shown to contain TUTase, RNA ligase, and gRNAs and remains stable after salt treatment. Depletion of endogenous cytochrome b gRNAs by the addition of complementary oligonucleotides in vitro completely inhibits editing-site cleavage of synthetic preedited cytochrome b mRNA. The addition of synthetic cognate gRNA for cytochrome b but not unrelated small RNA restores editing-site cleavage. These studies show that in addition to specifying the site and number of uridines added or deleted, gRNAs provide the necessary information for cleavage by the editing-site-specific endonuclease.

Time trends of haemoglobin levels and anaemia prevalence in infancy in a total community.

In order to determine the trends in haemoglobin (Hb) levels and the prevalence of anaemia in infancy in an entire community, 3,147 infants aged 9-11 months attending the Mother and Child Health Clinics of the teaching and research Health Center in Kiryat Hayovel, Jerusalem, were examined. From 1971 to 1979 infants diagnosed as anaemic were given treatment. From 1980 to 1988 supplement was given to all infants from the age of 3 to 12 months. There was a mean increase of 0.6 g/dlHb between the two periods, with a larger increase in the Hb levels in 1980-88 as compared to 1971-79 (P = .0001). The prevalence of anaemia less than 11 g/dlHb decreased from 36% in 1971 to 27% in 1979 and to 19% in 1988. The prevalence of anaemia less than 10 g/dlHb decreased from 13.7% in 1971 to 8.7% in 1979 and to 3.6% in 1988. The time trend is probably due to changes in the socio-demographic characteristics of the population, an overall change in infant feeding practices in relation to iron source and the supplementation programme.

Effectiveness of iron supplementation compared to iron treatment during pregnancy.

This study presents the evaluation of an iron supplementation program in a community by comparing 478 pregnant women who received iron supplementation from the 4th month of pregnancy, with 392 pregnant women who received iron treatment only if their Hb level was less than 12 gm/dl, and had no supplementation. In the supplementation group, no statistically significant associations were found between compliance with age, education, social class or parity. Pregnant women of European-American origin showed higher rates of good compliance than those of Asian-African origin. The mean decrease of haemoglobin (Hb) and haematocrit (Hct) between the second and third trimester of pregnancy was smaller in the supplementation group (-0.9 gm/dl Hb, -2.1% Hct) than in the treatment group (-1.1 gm/dl Hb; -3.3% Hct). The differences between the two groups were significant only for the Hct levels (P = 0.022). The mean Hb and Hct levels during the third trimester of pregnancy were higher for good compliers (11.7 gm/dl Hb; 33.6% Hct) than for poor compliers (11.4 gm/dl Hb, 32.6% Hct).

Process and outcome evaluation of preventive care for infants in two types of practices.

Process and outcome of preventive and promotive infant care have been evaluated in a maternal and child health (MCH) service and compared with that of a comprehensive care family practice (FP), both serving a low middle class population in West Jerusalem. Both services are provided by the Community Health Center of the Department of Social Medicine. Community oriented primary care is integrated into the practices, including ongoing surveillance of the communities' health status. Preventive and promotive programs have been developed, implemented and evaluated. The process evaluation indicated a similar use of the preventive service in the MCH and FP services. Some of the routines were carried out to a lesser extent in the FP than in the MCH framework, such as growth monitoring, hearing tests and advice on iron supplementation. The small difference in compliance with routines did not affect a child's growth between birth and one year of age, but the anemia rate in the FP practice was higher than in the MCH practice. The high level of care and relatively small differences in process and outcome between the two types of services have been achieved by ongoing inservice training, a high level of personnel, similar protocols and supervision in both practices.

Effect of maternal vaccination on the susceptibility of growing pigs to leptospiral infection.

Serum samples were collected from 30 piglets, derived from 17 litters, whose dams had been vaccinated against leptospirosis. Microscopic agglutination test (MAT) titres against Leptospira interrogans serovar pomona varied greatly from pig to pig; there was less variation among littermates. Titres declined between 4 and 10 weeks of age, with an uncorrected half-life of 15.5 days, consistent with IgG being the main antibody class involved. Twelve pigs, 4 derived from unvaccinated sows and 8 from sows vaccinated against leptospirosis, were challenged intravenously at 8 weeks of age with leptospires of serovar pomona. Colostrum-derived antibody protected 4 out of 8 pigs, and in 1 of the remaining 4 the serological response was reduced. Three of the protected pigs showed reduced serological responses and in the fourth the response was strong, but delayed. All of the pigs derived from unvaccinated sows developed leptospiraemia and leptospiruria and showed strong serological responses. Protection by colostrum-derived antibody bore an inexact relationship to MAT titre, but a titre of 16 appeared to be sufficient for protection.

Use of iron supplements in infancy: a field trial.

Iron-deficiency anaemia in infancy, which is an important public health problem even in countries where gross malnutrition is not prevalent, can be prevented by iron supplementation or by fortification of infant foods with iron. A programme of iron supplementation was carried out in two places in Israel through the Maternal and Child Health services in the course of their routine duties. Though 89% of the mothers complied and gave iron supplements to their infants for a period of 1-9 months, only 26% continued for the full 9 months. A stastically significant difference was found in the haemoglobin and mean erythrocyte volume levels between the iron-supplemented group and the controls. The results indicate that the use of a higher daily dose of iron for a shorter period might lead to better compliance and greater benefits.

Glycolipoprotein cytotoxin from Leptospira interrogans serovar copenhageni.

Lipopolysaccharide (LPS), glycolipoprotein (GLP) and lipid extract were prepared from Leptospira interrogans serovar copenhageni. GLP, lipid extract or purified fatty acids from lipid extract produced cytotoxic effects seen as cell enzyme leakage followed by cytotoxic death when tested in mouse fibroblast L929 cells in tissue culture. All extracts also agglutinated mouse erythrocytes but purified LPS was not cytotoxic. Neither GLP nor LPS were pyrogenic but both gelled Limulus amoebocyte lysate. Specific anti-GLP IgG neutralized the cytotoxic and haemagglutinating effect of GLP; however, at higher concentrations it enhanced the cytotoxicity of GLP and mediated lysis of the erythrocytes. A high dose of leptospires (i.e. 10(10) organisms) killed weanling mice causing pathological changes similar to those seen in acute leptospirosis. Similar results were obtained with live, dead, pathogenic and saprophytic leptospires. The results suggest that toxicity is involved in leptospiral infection and that lipid components either of whole leptospires or of a leptospiral GLP may contribute to the pathogenesis of acute leptospirosis.

Evidence for gamma-aminobutyric acid modulation of ovarian hormonal effects on luteinizing hormone secretion and hypothalamic catecholamine activity in the female rat.

Recent evidence suggests that gamma-aminobutyric acid (GABA)-containing neurons may inhibit LH release under certain circumstances. The present experiments tested whether GABA agonists block the LH surge induced in ovariectomized rats by estradiol benzoate (EB) plus progesterone (P) treatment and whether these agents affect the concentration and turnover of hypothalamic catecholamines, assessed from the depletion that occurs after synthesis inhibition. Ovariectomized rats received EB, followed 2 days later by P. Simultaneously with P, rats received either saline or one of the GABA agonists, baclofen or muscimol. Other agonist-treated rats received a second injection 4 h later or were additionally treated with the postsynaptic GABA antagonist bicuculline. Additional experiments tested the effects of these agents on LH release in response to exogenous LHRH. The LH surge induced by EB plus P was blocked by administration of either baclofen or muscimol in a dose-dependent manner. Bicuculline did not prevent the effect of baclofen, but partially prevented the effect of muscimol. Neither baclofen nor muscimol significantly affected LH release in rats receiving LHRH. In a second set of studies in EB plus P-treated rats, baclofen and muscimol decreased the steady state concentrations of norepinephrine in the medial preoptic area and medial basal hypothalamus for several hours and markedly decreased the turnover rate of norepinephrine in these areas. The concentrations and turnover of epinephrine were also decreased by these GABA agonists in the medial basal hypothalamus. The drugs had no effect on dopamine levels or turnover in either structure. These results support the hypothesis that a GABAergic system regulates LH release via modulation of noradrenergic and adrenergic systems that control LHRH secretion.

Regional differences in mu 1-binding of [3H][D-Ala2,D-Leu5]-enkephalin: comparisons of thalamus and cortex in the rat.

Typically, mu 1-sites represent approximately 25-35% of binding in rat brain homogenates. Competition studies indicated that approximately 60% of [3H][D-Ala2,D-Leu5]-enkephalin ([3H]DADLE) binding in the thalamus was inhibited by low concentrations of morphine (2-5 nM). This high proportion of mu 1-binding was anticipated based upon the low levels of delta-sites and the high levels of mu 1-sites in this region observed in autoradiography studies. In contrast, morphine lowered [3H]DADLE binding by only approximately 5-15% in the cortex, a region known to possess large amounts of delta- and few mu 1-receptors. These results support previous autoradiography studies and illustrate the advantages of using tissue regions in the characterization of opiate receptor subtypes.

Modulation of luteinizing hormone release and catecholamine activity by opiates in the female rat.

Previous studies have shown that the stimulation of LH release by the opiate receptor blocker, naloxone, can be prevented by catecholamine synthesis inhibitors, suggesting opiate regulation of catecholamine release. The present study tested whether an opiate agonist and antagonist would affect the depletion of hypothalamic catecholamines observed after synthesis inhibition, as a measure of catecholamine activity, concomitant with changes in LH secretion. Administration of naloxone to estradiol-primed rats increased LH release and potentiated the depletion of norepinephrine in the preoptic-anterior hypothalamus and medial basal hypothalamus, and enhanced the decline of epinephrine and of dopamine in the medial basal hypothalamus, suggesting increased catecholamine activity in these regions. Administration of the opiate agonist, morphine, to estrogen/progesterone pretreated females decreased LH and decreased the depletion of the catecholamines in the above mentioned areas, suggesting reduced activity. In most cases, naloxone antagonized the inhibitory effect of morphine. These findings indicate that naloxone may stimulate LH release by enhancing hypothalamic catecholamine turnover, possibly by removing the inhibitory influence of an endogenous opioid neuropeptide.

Evidence that norepinephrine and epinephrine systems mediate the stimulatory effects of ovarian hormones on luteinizing hormone and luteinizing hormone-releasing hormone.

Results from previous investigations have suggested an important role for central epinephrine (EPI) systems in mediating the stimulatory effects of ovarian hormones on LH release in ovariectomized female rats. The purpose of these experiments was 1) to test whether selective inhibition of EPI synthesis blocks the sequential accumulation and decline of LHRH concentrations in the median eminence that precedes the ovarian hormone-induced LH surge and 2) to test whether the stimulatory ovarian hormone regimen enhances the activity of EPI systems in the hypothalamus. Ovariectomized rats were treated with estradiol, followed 2 days later by progesterone. Animals were treated before progesterone administration with saline, one of the EPI synthesis inhibitors [SK&F 64139 (2,3-dichloro-tetrahydroisoquinoline HCl) or LY 78335 (dichloro-alpha-methylbenzylamine)], or the dopamine-beta-hydroxylase inhibitor FLA-63 (bis-4-methyl-1-homopiperazinyl thiocarbonyl disulfide), which inhibits NE and EPI synthesis. The catecholamine synthesis inhibitors blocked or delayed the afternoon LH surge. FLA-63 completely prevented the accumulation of LHRH in the median eminence that preceded the rise in LH release. However, selective EPI synthesis inhibition with SK&F 64139 only partially prevented this increase in LHRH. A second EPI synthesis inhibitor, LY 78335, delayed both the LH surge and the rise in LHRH. In a second experiment, the administration of estradiol and progesterone to ovariectomized rats increased the alpha-methyltyrosine-induced depletion of hypothalamic EPI, suggesting increased activity in this system during the LH surge. Further experiments localized this effect to the medial basal hypothalamus. The depletion of both NE and EPI after synthesis inhibition was also enhanced during an earlier period, approximating the time of LHRH accumulation. These results suggest that the ovarian hormones activate both NE and EPI systems to stimulate the early afternoon rise of LHRH in the median eminence and to induce the subsequent LH surge.