Postcopulatory effects of two antifertility agents on ova transport and implantation

The daily doses which prevented implantation in 50 percent of treated animals (ED50) of 2,3 - bis (4-hydroxyphenol) valeronitrile (SC-3402) and 2,3 - bis (4-methoxyphenyl) pent-2-enenitrile (SC-3296) injected in rats s on Days 1 to 3, or Days 4 to 7, or Days 1 to 7 (Day 1 = pregnancy) were 100, 200, and 40 mcg and 50, 100, and 12 mcg respectively, ED50 doses of estrone were 4,8 and 3.5 mcg. Control animals showed ova in the oviduct only on Days 1, 2 and 3, also in the uterus on Day 4, and only in the uterus on Day 5. Very few ova were found in rats treated with 10 mcg estrone daily Day 1-2 and autopsied on Day 3. The same treatment period with 200 mcg SC-3402 caused similar results. 64 mcg SC-3402 resulted in a smaller reduction of ova. Acceleratory potency of 200 mcg SC-3402 is greater than can be due to its estrogenic activity equivalent, 0.5 mcg estrone; that of 64 mcg SC-3296 (4.8 equivalents estrone) can be so ascribed. Rats receiving daily 4-8 mg 17 alpha-acetoxy-6 alpha-methylprogesterone (MAP) from Day 1 to 9 to delay nidation, and 200 mcg SC-3402, autopsied on Day 10 showed no free blastocysts and a few implantation sites in the process of resorption (Free blastocysts were found in rats similarly treated but with ligation of the uterus at the cervix on Day 5 to prevent expulsion of blastocysts). Control rats on Day 10 showed a few implantation sites and free blastocysts. The normal number of implantations were present in SC-3296 treated rats. The average weight of cornu traumatized by threading one cornu in psuedopregnant rats with a silk thread on Day 5 (Day 1=cervical stimulus) in rats treated with 200 mcg SC-3402 on Days 5-8, 404 plus or minus 50 mg was significantly (P less than .05) lower than mean control weight, 794 plus or minus 48 mg. The difference between the mean weight of non-traumatized cornu of rats given 100 mcg, 284 plus or minus 36 and 232 plus or minus 12 mg respectively was significantly (P less than .05) greater than in controls, 159 plus or minus 5.8 mg. The deciduoma-inhibiting activity of SC-3402 is further evidence that it initiates nidation but impedes early implantation stages.     

Complex of recombinant heat shock protein with lipopolysaccharide induces rapid protection of mice against Salmonella typhimurium and avirulent for humans avian influenza virus H5N2

Protective effect of immunization with heat shock protein (HSP) against bacterial and viral infections in mice was studied. Recombinant HSP 70 kDa of Mycobacterium tuberculosis contaminated with lypopolysaccharide (0.185 mcg/ml) was used for experiments. One intraperitoneal injection of 100 or 400 mcg of HSP induced rapid protection against intraperitoneal challen e with 125 LD50 of Salmonella typhimurium (on 3rd-6th day) and against intranasal challenge with 10 LD50 of avirulent for humans avian influenza virus H5N2 (A/ mallard/Pennsylvania/10218/84) (on 5th-8th day). Three daily injections with 10 mcg of HSP induced rapid, significant and long-term protection against S. typhimurium. Immunization with HSP protected 100% of mice during 3 days after the challenge, 50% of immunized animals survived during 21 days (duration of the study). All nonimmunized mice died on 6th day.     

Sex chromosome variation and cytotaxonomy of the onchocerciasis vector Simulium squamosum in Cameroon and Nigeria

On the basis of sex chromosome variation, three cytotypes of Simulium squamosum (Enderlein) (Diptera: Simuliidae) are described from Cameroon and Nigeria. Simulium squamosum A is the typical form as originally described by Vajime & Dunbar (1975) with chromosome I as the sex chromosome. It occurs throughout most of Cameroon and south-east Nigeria. A second cytotype, S. squamosum B, is described from the river Sanaga (Cameroon). It also has chromosome I as the sex chromosome, but the nature of the sex differential region is different. Simulium squamosum C has no sex-linked chromosomal rearrangements. It is widespread in Nigeria and occurs near Mount Cameroon, where it seems to hybridize with S. squamosum A.     

Prevalence of multi-drug resistant Salmonella typhi among clinically diagnosed typhoid fever patients in Lagos, Nigeria

A total of 635 clinically diagnosed typhoid fever patients were bled from three different health institutions in the metropolis of Lagos, Nigeria over a period of 15 months, May 1997 to July 1998. Out of the total blood cultured, 101 (15.9%) isolates of Salmonella species were isolated of which 68 (67.3%) were S. typhi, 17 (16.8%) and 16 (15.8%) were S. paratyphi A. and S. arizonae respectively. The overall isolation rate of S. typhi among patients is 10.7%, with most isolates 45.9% found among the severely-ill young adults, age group 16-30 years. All isolates were subjected to anti-microbial susceptibility testing using 12 different antibiotics: chloramphenicol, ampicillin, cotrimoxazole, gentamicin, colistin sulfate, nalidixic acid, nitrofurantoin, cefotaxime, tetracycline, streptomycin, ofloxacin and ciprofloxacin. All the S. typhi and S. paratyphi A isolates showed resistance to two or more of the 10 of 12 antibiotics tested particularly the 3-first-line antibiotics commonly used (chloramphenicol, ampicillin and cotrimoxazole) in the treatment of typhoid fever in Nigeria. No isolate showed resistance to ofloxacin and ciprofloxacin, however, nalidixic acid and gentamicin showed a moderate and appreciable inhibition to most of our isolates.     

The effect of fractionated exposure to unequal concentrations of chemical mutagens

The effect of unequally fractionated concentrations of dipin and thiophosphamid on chromosomes of human lymphocytes was investigated at Go phase. There were used five low concentrations of mutagens 2, 0.2, 2.10(-2), 2.10(-3), 2.10(-4) mcg/ml and one high concentration 20 mcg/ml by which cells have been treated. Decrease of chromosome breaks and exchanges were observed, but the level of the aberration cell was stable. The "protective" levels for dipin were in concentrations of 0.2, 2.10(-2), 2.10(-3) mcg/ml. Only one "protective" concentration was 2.10(-2) mcg/ml.     

Effect of estrogen on biochemical composition of the rat seminiferous tubules

This study concerns the effect of graded doses of estrogen, alone or in combinations with progesterone, on the biochemical composition of the rat seminiferous tubules. Data on the accessory genital organs and pituitary gonadotrophic activity are added. Adult male albino rats received estradiol dipropionate (.1, 1 and 5 mcg/rat) injected intramuscularly, in .1 ml olive oil, daily for 30 days. Animals given the 5 mcg dose were given a 30 day rest period to determine reversibility of effects. In another group estrogen (5 mcg/rat) and progesterone (1 mg/rat) were given concurrently but at different sites for 30 days. Controls received vehicle only. Animals were sacrificed 24 hours after the last injection or rest period and genital organs and the pituitary were removed for study. A progessive reduction in testis weight with dosage was found after estrogen or the combination (p is less that .01). The low dose (.1mcg) had an inconsistent effect on spermatogenesis and endocrine function of the testis. Diameter of the tubules was reduced. Spermatogenesis was arrested in 25% of the tubules at the spermatid of secondary spermatocyte stage. Some normal spermatozoa were seen. Tunica propria was thickened. Some Leydig cells showed atrophy. Vascularity was increased. The median dose (1 mcg) caused spermatogenic arrest at the spermatid or secondary spermatocyte stage but the Sertoli cells were prominent. Only a few spermatozoa were seen. There was some desquamation of seminiferous epithilium. Tubular diameter was still further reduced and the tunica propria thickened. Leydig cells were atrophied. Few spermatozoa were found although 25-30% showed some spermatogenesis. The high dose (5 mcg) caused marked reduction in the diameter of the tubules. Spermatogenesis was arrested at the primary spermatocyte or spermatogonial stage. The tunica popria was much thickened. There was much desquamation and tubular lumeus were filled with debris. The Sertoli cells were hypertrophied. The Leydig cells were atrophied. The tunica albuginea was thickened. There were no spermatozoa. In the recovery group estrogen effects had disappeared, but the tubular diameter remained reduced. Tunica propria was normal. Spermatogenesis progressed to the spermatid stage and in 50% of the tubules many spermatozoa were present. The Leydig cells appeared normal. However spermatozoa were not found in the vas defereus. The histological appearance of the teatis in the estrogen and progesterone group was of the high dose estrogen type but with arrest of spermatogenesis at the spermatid, spermatocye or spermatogonial stage. The Sertoli cells remained hypertrophied. Leydig cells were atrophic. The large blood vessels were engorged. Weight of organs returned almost to normal. Estrogen .1 and 1 mcg had no effect on pituitary weight or gonadotrophin content. The high dose (5 mcg) alone or with progesterone caused a significant increase in pituitary weight (p is less than .0). Estrogen alone (5 mcg) caused a significant decline in pituitary gonadotrophin content (p is less than .0) but the combined therapy had no effect. None of the biochemical constituents of the seminiferous tubules showed any change after injection of .1 mcg of estrogen but 1 mcg dose caused an increase in protein nitrogen, alkaline phosphatase activity and total lipids. The high dose (5 mcg) provoked higher levels.     

Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandin F2alpha

The contractile response of the midpregnant human uterus to a new (PG) prostaglandin analogue, 15(S)-methyl-PGF2alpha (15-me-PGF2alpha), was investigated and compared to the effect of natural PGF2alpha. It was found that the threshold dose of 15-me-PGF2alpha was around 10 mcg when given as a single intravenous injection, which is approximately 1/10 of the corresponding dose of PGF2alpha. It was also found that higher intravenous doses of 15-me-PGFalpha resulted in a uterine response of longer duration than that following PGF2alpha. Intramuscular injection of the analogue at doses of 1.0-1.5 mg induced a marked uterine stimulation sustained for 5-7 hours without causing local reaction. Intravenous infusion of 5 mcg/min of 15-me-PGF2alpha stimulated a level of uterine activity equivalent to that of 75 mcg/min of PGF1alpha. The incidence of gastrointestinal side effects was the same in the 2 treatment groups. However, there seemed to be a tendency toward a significantly higher abortion rate with the analogue.     

Evidence for late Pleistocene population expansion of the malarial mosquitoes, Anopheles arabiensis and Anopheles gambiae in Nigeria

Anopheles gambiae Giles s.s. and Anopheles arabiensis Patton (Diptera: Culicidae) are major vectors of malaria in Nigeria. We used 1115 bp of the mitochondrial COI gene to assess their population genetic structures based on samples from across Nigeria (n = 199). The mtDNA neighbour-joining tree, based on F(ST) estimates, separated An. gambiae M and S forms, except that samples of An. gambiae M from Calabar clustered with all the An. gambiae S form. Anopheles arabiensis and An. gambiae could be combined into a single star-shaped, parsimonious haplotype network, and shared three haplotypes. Haplotype diversity values were high in An. arabiensis and An. gambiae S, and intermediate in An. gambiae M; all nucleotide diversities were relatively low. Taken together, patterns of haplotype diversity, the star-like genealogy of haplotypes, five of seven significant neutrality tests, and the violation of the isolation-by-distance model indicate population expansion in An. arabiensis and An. gambiae S, but the signal was weak in An. gambiae M. Selection is supported as an important factor shaping genetic structure in An. gambiae in Nigeria. There were two geographical subdivisions in An. arabiensis: one included all southern localities and all but two central localities; the other included all northern and two central localities. Re-analysing an earlier microsatellite dataset of An. arabiensis using a Bayesian method determined that there were two distinctive clusters, northern and southern, that were fairly congruent with the mtDNA subdivisions. There was a trend towards decreasing genetic diversity in An. arabiensis from the northern savannah to the southern rainforest that corroborated previous data from microsatellites and polytene chromosomes.     

LH- and FSH response to long-term application of LH-RH analogue in normal males.

The effect of luteinizing hormone-releasing hormone (LHRH) analogue after subcutaneous application over a 12-day period was evaluated in 15 normal males to determine whether gonadotropin secretion is influenced by longterm application. After 1.25 mcg/day, LH increases were measurable 3 hours after daily receipt of the analogue. After 2.5 mcg/day, the release of LH secretion was even greater, although this stimulation was markedly reduced in the 2nd week. After 5 mcg in 2-day intervals, a clearly induced LH increase was observed on the day of administration and was maintained for 10 hours. Similar results were noted for follicle-stimulating hormone (FSH). There was a response of FSH after 1.25 mcg and 2.5 mcg, but this response decreased in the 2nd week. After application of 5 mcg every other day, there was a consistent FSH increase that subsided on the treatment-free day and continued into the 2nd week of treatment. These findings suggest that LHRH analogues should be administered in low doses subcutaneously or intranasally at daily intervals to enable a longterm effect on gonadotropin release.     

Effect of L-lysine-alpha-oxidase gel on development of ophthalmic herpes and herpetic skin lesions in rabbit]

The effect of various doses of L-lysine-alpha-oxidase gel (1.4-3.5 and 70 mcg/ml) on development of eye and skin herpetic lesions due to type 1 herpes simplex virus was studied on rabbits. The doses of 1.4 to 3.5 mcg/ml were not sufficient for the therapeutic effect. The dose of 70 mcg/ml provided complete healing of the lesions in 3 to 4 days. The results were confirmed by the immunological tests.     

The cytotoxic effect of heavy metals on an L-cell culture

The dependence of some parameters of L-cells culture viability on different concentrations of heavy metals was studied. Considerable cytotoxic effect of low concentrations of nickel (0.025 mcg/ml) and lead (0.05 mcg/ml) was shown. Copper and chrome at concentrations of 0.25-0.5 mcg/ml promote cells proliferation between third and fifth days of cultivation. Nickel at concentration 0.025 mcg/ml and lead at all investigated concentrations synchronize cells division in culture. Increasing of giant polynucleas cells level in culture was characteristic for investigated metals. The maximum levels of this type cells were caused by the action of nickel, chrome and copper.     

Reduction in magnetic resonance imaging T2 burden of disease in patients with relapsing-remitting multiple sclerosis: analysis of 48-week data from the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study

Background  

The EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study was an international, randomized, open-label, assessor-blinded, parallel-group study assessing the efficacy and tolerability of interferon (IFN) beta-1a, 44 mcg subcutaneously (sc) three times weekly (tiw), and IFN beta-1a, 30 mcg intramuscularly (im) once weekly (qw), in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this analysis was to assess whether reductions in T2 burden of disease (BOD) were greater for patients receiving IFN beta-1a, 44 mcg sc tiw, than for those treated with IFN beta-1a, 30 mcg im qw, and to assess the impact of neutralizing antibodies (NAbs).     

Determination of antibiotic chemicals using microbiological tests: evaluation of the limits of sensitivity]

Sensitivity of Bacillus subtilis BGA and Bacillus stearothermophilus var. calidolactis disc assays to 53 chemio-antibiotics was tested. Test-microorganisms were sown in two different mediums: PM Indicator Agar, Difco U.S.A., and Standard II Nutrient Agar, Merck Germany, modified according to Nouws. The mediums were used with or without addition of Trimethoprim (at a concentration of 0.12 or 0.024 mcg/ml of medium for B. subtilis and for B. stearothermophilus respectively). B. stearothermophilus did not grow in Standard II. However, the B. subtilis assay gave the best results with Standard II, apart for aminoglycosides. The B. stearothermophilus disc assay was the most sensitive to penicillins (Minimum Inhibiting Concentration in mcg/ml, MIC, between 0.001 and 0.004), cephalosporins (MIC between 0.003 and 0.09, apart from Ceftazidime, 0.3) and aminoglycosides (MIC between 0.03 and 0.6). The B.subtilis disc assay showed better sensitivity to quinolines (MIC between 0.05 and 4) and to some tetracyclines (oxytetracycline and chlortetracycline, MIC 0.03). Trimethoprim, where added, determined a higher sensitivity to sulfonamides (MIC between 0.025 and 0.25).     

Sex and Age Differences in Levothyroxine Dosage Requirement

ObjectiveTo examine the performance of weightbased formulae for estimating the levothyroxine dosage requirement in athyreotic patients and to determine whether formula performance is affected by age, sex, or menstrual status.MethodsIn this prospective study, euthyroid study participants aged 18 to 65 years were followed up after total thyroidectomy at 4 time points: 6-8 weeks, 12-16 weeks, 6 months, and 1 year. Patient weight, serum thyrotropin concentration, and levothyroxine dosage required were recorded at each time point. The postoperative starting levothyroxine dosage was 1.7 mcg/kg daily for patients with benign thyroid disease and 2.2 mcg/kg daily for patients with thyroid cancer. Actual body weight was used to calculate the initial dosage. At steady state, adjustments were made in each patient’s levothyroxine dosage until the target thyrotropin concentration was reached. The levothyroxine dosage required to achieve this goal was documented.ResultsFifty patients were included (37 women, 13 men). Formulae based on actual body weight were accurate in achieving a normal thyrotropin concentration in 48% to 75% of participants. Final dosages to achieve normal thyrotropin values were similar in men (1.43 mcg/kg daily) and menopausal women (1.68 mcg/kg daily), but higher in premenopausal women (2.10 mcg/kg daily). When a formula based on ideal body weight was used, the requirement for menopausal women (2.34 mcg/kg daily) was similar to that of premenopausal women (2.44 mcg/kg daily), but the requirement for men (1.73 mcg/kg daily) remained lower than that observed in both female groups.ConclusionsWhen actual body weight was used to calculate levothyroxine dosage requirement, premenopausal women appeared to have a greater requirement than either menopausal women or men. When ideal weight was used, the requirement of all women was greater than that of men. Perhaps with formulae using actual weight, this apparent sex difference is masked by the greater weight, older age, or altered hormonal milieu of menopausal women. (Endocr Pract. 2010;16:71-79)     

Once-daily fluticasone furoate/vilanterol 100/25 mcg versus twice daily combination therapies in COPD – mixed treatment comparisons of clinical efficacy

Background

Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily inhaled corticosteroid (ICS)/long-acting beta₂ agonist (LABA) treatment approved in the United States, Canada and Europe for the long-term maintenance therapy of COPD. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI against established twice-daily ICS/LABA combination therapies on clinical efficacy outcomes.

Methods

Data from 33 parallel-group randomised controlled trials (RCTs) of ICS/LABAs, of ≥8 weeks’ duration in patients ≥12 years of age with COPD, identified by systematic review, were analysed using covariate-adjusted Bayesian hierarchical models for three efficacy outcomes. Lung function, assessed by change from baseline in forced expiratory volume in one second (FEV₁), was the outcome of primary interest (n = 28 studies). Secondary objectives were assessment of annual rate of moderate/severe exacerbations (n = 15) and patient-reported health status, measured by change from baseline in St George’s Respiratory Questionnaire (SGRQ) Total score (n = 20). Overall, 25 different treatments were included in the MTC; we report findings, including probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and budesonide (BUD)/formoterol (FORM) 400/12 mcg.

Results

For FEV₁, FF/VI 100/25 mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg using a 50 mL margin. For annual rate of moderate/severe exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a 10% rate ratio margin. For SGRQ Total score, the corresponding probabilities of non-inferiority were 99% and 98%, respectively, on a 2-unit margin. Significant covariate effects were identified: increased age was associated with deterioration in FEV₁ and reduced exacerbation frequency; shorter study duration was associated with reduced exacerbation frequency.

Conclusions

FF/VI 100/25 mcg was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function and health status outcomes. Non-inferiority on moderate/severe exacerbation rate was not demonstrated to the same degree of confidence, though observed rates were similar. Model limitations include a weak treatment network for the exacerbation analysis and variability across the included studies. Our data support previous RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function and health status in COPD is comparable with twice-daily ICS/LABAs.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0184-8) contains supplementary material, which is available to authorized users.     

Schistosoma curassoni Brumpt, 1931 and S. bovis (Sonsino, 1876) in cattle in northern Nigeria

Schistosoma curassoni has been recovered from cattle in northern Nigeria. Rectal scrapings of 90 cows slaughtered at the Kano abattoir, Kano, Nigeria during March and April 1986 revealed a prevalence of 7.8% S. bovis and 2.2% S. curassoni. Further examination of the mesenteric and rectal veins of 502 cows showed that the overall prevalence of schistosomiasis was 31.1%. Local Bulinus globosus were infected successfully in the laboratory with s. bovis miracidia.     

Azithromycin levels in the chorion tissue within the first three months of the pregnancy term]

The levels of azithromycin in the chorion tissue within the first 3 months of the pregnancy term (42 to 56 days post coitus) were determined. Three days after the use of azithromycin (Sumamed) the antibiotic concentration in the villi tissue was 0.065 to 0.26 mcg/mg (the average of 0.129 mcg/mg). The azithromycin concentration above 0.125 mcg/mg was detected in 38.5% of the women. The results confirmed the fact of significant azithromycin accumulation in the chorion tissue. The percentage of the azithromycin transplacental transfer within the above mentioned pregnancy term varied from 2.3 to 9.3 (the average of 4.6).     

The relevance of the pharmacologic properties of a progestational agent to its clinical effects as a combination oral contraceptive

Levonorgestrel (LNg) is known for its marked progestational/contraceptive activity. As shown in animal experiments, however, high doses of LNg are required to elicit an androgenic response; in contrast, considerably lower doses of LNg are required for antiovulatory (contraceptive) action. Thus, a large dose separation exists between androgenic and contraceptive activity. When LNg is combined with an estrogen, as in the contraceptive formulations, the androgenic response is attenuated or negated. The results of recent clinical trials have demonstrated that the androgenic activity of LNg is not expressed at contraceptive doses, particularly when LNg is combined with ethinyl estradiol (EE), as in the low-dose monophasic/triphasic formulations (monophasic [Nordette]: 150 mcg LNg/30 mcg EE; triphasic [Triphasil/Trinordiol]: six days, 50 mcg LNg/30 mcg EE; five days, 75 mcg LNg/40 mcg EE; ten days, 125 mcg LNg/30 mcg EE). Clinical evidence from several trials confirms that sex hormone-binding globulin levels are increased, plasma androgen levels are decreased, and acne is markedly improved with the use of Triphasil and Nordette, suggesting a non-androgenic profile.     

Endocrine control of clutch size in reptiles. VIII. antiestrogenic effects of clomiphene citrate in the lizard Anolis carolinensis

The influence of clomiphene citrate on follicle-stimulating-hormone (FSH) and estradiol-induced growth of ovarian follicles and oviducts in the lizard A. carolinensis was studies. In Experiment 1 lizards received 14 daily injections of either saline, clomiphene (1, 10 or 20 mcg), or FSH (1 or 10 mcg) or combined clomiphene-FSH treatment. In Experiment 2, adult lizards with hypertrophied, vitellogenic ovaries, and enlarged oviducts, weres adenohypophysectomized and treated with a daily dose of .05 ml of either saline, saline plus 5 mcg clomiphene, saline plus 10 mcg FSH, saline plus 10 mcg estradiol-17beta, or FSH plus clomiphene or estradiol plus clomiphene. FSH increased follicle size in previtellogenic ovaries. Injection of 1 mcg clomiphene reduces the effects of FSH. 20 mcg clomiphene given alone stimulated the growth of larger follicles. Clomiphene blocked FSH-induced appearance or maintenance of large (less than 2.0 mm) vitellogenic follicles. It blocked FSH gains in oviductal weight and well as stimulated growth of small previtellic follicles. Estradiol-induced follicular and oviductal growth was uneffected by clomiphene. While low doses of clomiphene are antiestrogenic they are unable to combat the effects of high dose estradiol.