Atypical Hypocortisolism

ObjectiveTo report a patient who had developed reversible hypocortisolism during the use of quetiapine.MethodsEarly morning cortisol levels were measured on two separate days. In addition, the patient underwent testing with intravenous synthetic adrenocorticotropic hormone (1 mcg tetracosactide) before and after tapering of quetiapine. Pituitary function was assessed and magnetic resonance imaging (MRI) was performed.ResultsThe patient had low early morning cortisol levels at presentation when using quetiapine. Tetracosactide testing indicated hypocortisolism. A MRI of the pituitary was unremarkable. The patient was treated temporarily with hydrocortisone and quetiapine was tapered. After quetiapine had been discontinued, the patient’s cortisol production had returned to normal.ConclusionAlthough lowering cortisol levels has been previously reported, this is the first report of hypocortisolism associated with the use of quetiapine. It is possible symptoms of malaise in patients who use quetiapine could be attributed to quetiapine-related hypocortisolism. (Endocr. Pract. 2013;19:e112-e114)     

Qualitative and quantitative data on experimental luteinization in the female rat

The dose-effect of 1.5-16 mcg luteinizing hormone (LH) per 100 gm body weight injected in rats at 1100-1200 on proestrus was compared with 30 mg meprobamate given to controls at the same time, on luteinization and ovulation seen in serial ovarian sections. The WII Wistar rats were killed. Luteinization with or without ovulation increased with dose (1.5, 3, 5, 8, and 16 mcg) of LH to a plateau (90%) above the 5 mcg dose, compared with 18% in controls. 2-5 animals in each dose group had preluteinized follicles, characterized by a dissociation of the cumulus oophorus from the granulosa. The absolute frequency of ovulation increased linearly with LH dose, but the frequency of ovulation among rats that luteinized was invariant. The coefficient of ovulation, calculated as the mean incidence of ovulation in relation to the total number of luteinized or preluteinized follicles in each rat, decreased from .769 in controls to .580 in the 3 mcg group, then rose to .916 in the 16 mcg group. Thus, in proestrous rats, low doses of LH induce corpora lutea with retained ova. The threshold dose of LH for luteinization and for ovulation is lower in proestrus than in diestrus II, but varies slightly in different strains of rats.     

Alternating consecutive maximum contractions as a test of muscle function

Although regularly used, the standard strength test (SST) is known to have several shortcomings, such as being based only on sustained maximum forces, and on a relatively large number of trials that expose the tested muscle to rapid fatigue. The purpose of this study was to evaluate alternating consecutive maximum contractions (ACMCs) as a test of the muscle function through its comparison with SST. Twenty-four participants performed both the externally paced isometric ACMC (i.e., series of consecutive maximum force exertions in 2 directions) and SST of the knee extensor and flexor muscle. The derived variables of both tests included the knee extensor and flexor peak forces (PFs) and their maximum rates of development. Movement speed and muscle power output were also assessed through standard maximum performance tests. Both ACMC and SST revealed on average high intratrial (intraclass correlation coefficient [ICC] > 0.80) and moderate-to-high test-retest reliability (ICC > 0.60), and significant (p < 0.05) positive relationships among the PFs and their rates of development of the tested muscles. The variables of both tests also suggested on average moderate correlations with the maximum performance tests. Finally, ACMC variables revealed relatively stable values across a wide range of frequencies including the 'self-selected' one. Although some properties of ACMC could be similar to SST, the important comparative advantages of ACMC could be relatively low and transitional maximum forces exerted, and fewer trials needed for testing 2 antagonistic muscles. Although further research is needed, particularly concerning the external validity and generalizability, we conclude that the ACMC represents a test of muscle function that could be applied either as an alternative or complementary test to SST.     

The influence of substance P central administration on ethanol intake in rats chronically exposed to alcohol

The influence of central substance P (SP) administration on alcohol intake and brain dopamine metabolism within mesocortico-limbic and nigrostiatal systems of rats exposed to ethanol, was studied. During 6 months, the rats consumed 15% ethanol solution instead of water. Central administration of SP (3 mcg/kg) decreased alcohol consumption by 41% in alcohol-preference animals. After long-term ethanol exposure ratios DOPAC/DA and HVA/DA were reduced in striatum and accumbens. SP in dose 3 mcg/kg increased content of DOPAC by 17% and HVA by 23% as well as DOPAC/DA by 9%, HVA/DA by 19% in accumbens. Whereas in striatum only increased DOPAC (28%) and HVA (29%) were observed as compared with saline-treated rats.     

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.     

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.     

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.     

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial

BackgroundLow syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China.Methods and findingsAn open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing.ConclusionsCompared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested).Trial registrationChinese Clinical Trial Registry: ChiCTR1900022409.

In a multi-arm randomized controlled trial, Cheng Wang and colleagues determine the effectiveness and cost of expanding syphilis self testing among men who have sex with men in China.     

A severe episode of wildlife-derived scabies in domestic goats in Italy

A scabies outbreak, with unusually high mortality and morbidity, occurred in a poorly managed goat flock in north-eastern Italy. The source of infection was traced back to contact with scabietic chamois (Rupicapra rupicapra) within a recognised sylvatic focus of the disease. Spill-over of scabies from chamois to goats is a matter of great concern to resource managers. Currently scabies-free populations of wild Caprinae in the central and western Alps may eventually be exposed to infected goats transported over long distances. Sanitation of the studied flock was obtained following three applications of pour-on moxidectin at an approximate dose of 500 mcg/kg. Follow-up included titration of circulating anti-Sarcoptes antibodies in a labelled avidin–biotin ELISA test. Two operators developed pseudoscabies after handling the infested flock.     

Prophylactic use of ceftriaxone in combination with F I antigen immunization in studies on uninbred albino mice infected by Yersinia pestis. Antiplague immunity development]

Administration of highly immunogenic (ED50 12.6 mcg/mouse) F I antigen (100 mcg/mouse) to albino mice 5 hours after their contamination approximately with 1000 LD50 of Yersinia pestis 231 provided 99-percent survival of same animals (17-50%) and 2-5-day prolongation of the life-span, that was indicative of the phenomenon analogous to the survival phenomenon observed in infected animals immunized by immunogenic strains of the plague microbe. The experiment on the mice confirmed high efficacy of ceftriaxone (100-percent survival) when used prophylactically for 5 days 5 hours after the contamination by Y. pestis 231 (approximately 1000 LD50) in the dose equivalent to the daily dose for humans. However, no antiplague immunity developed in the survivors: the immunity index (II) of 1.5x10. The use of ceftriaxone according to the same scheme simultaneously with single immunization by F I antigen in a dose of 100 mcg/mouse resulted not only in 100-percent survival of the animals but also in development of expressing antiplague immunity (II 2.2x10(5)). The protection level corresponded to the control with the same live-stock of the animals after a single immunization in the analogous dose of F I antigen (II 3.2x10(4)) and the ceftriaxone use (II 1.0x10(5)), as well as after immunization of the mice by 10(6) microbial cells of Y. pestis EV NIIEG (II 1.2x10(5)). The results of the study are indicative of the prospective use of subsingle vaccines of the new generation based on F I antigen for combined specific and urgent prophylaxis.     

Hypothalamo-pituitary dysfunction in patients with chronic subdural hematoma

Relatively frequent pituitary hormone deficiencies are observed after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) and according to the published studies the neuroendocrine consequenses of traumatic brain injury are underdiagnosed. In a cohort of 59 patients (49 males, mean age 68.3 years, 36-88 years) after evacuation of subdural hematoma (SDH) were evaluated hypothalamo-pituitary functions one week after surgery, after three months and after one year. Hypogonadism was present in 26 % of patients in an acute phase, but in the majority had a transient character. Less than half of patients was GH deficient (GHD) according to the GHRH+arginine test. We did not find any serious case of hypocortisolism, hypothyroidism, diabetes insipidus centralis nor syndrome of inappropriate secretion of ADH (SIADH). Transient partial hypocortisolism was present in two cases, but resolved. We did not find relation between extension of SDH or clinical severity and development of hypopituitarism. In conclusion, in some patients with SDH growth hormone deficiency or hypogonadism was present. No serious hypocortisolism, hypothyroidism, diabetes insipidus nor SIADH was observed. The possibility of neuroendocrine dysfunction should be considered in patients with SDH, although the deficits are less frequent than in patients after TBI or SAH.     

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.     

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.     

Screening of natural immunosuppressors by their ability to modify steroid synthesis in hepatocytes]

In the programme for screening sterol synthesis inhibitors with the use of actinomycetes and fungi 702 strains were tested. The effect of alcohol extracts of the mycelium of fungi and actinomycetes at a dilution of 1/10(3) on sterol synthesis by the Hep G2 hepatome cells was determined by incorporation of 3H acetate into sterols and proteins. Lovastatin (200 pg/ml) was used as the control: the sterol synthesis was decreased by 49 +/- 4% without inhibiting the protein synthesis. A number of the cultures produced compounds inhibiting under the experimental conditions the synthesis of sterols by 70 to 80% with simultaneous inhibition of the protein synthesis at least by 60 to 70%. Three compounds from that group produced by streptomycetes were subjected to a more detailed investigation. The compounds were demonstrated to be active antifungal antibiotics (MIC 0.1-1 mcg/ml). In a dose of 0.1-1 mcg/ml they showed high immunosuppressive activity in models of lymphocyte transformation in mice, whereas cyclosporin was active in a dose of 1 mcg/ml. Therefore, the model for screening hypolipidemic compounds could be considered useful for screening promising natural immunosuppressors.     

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.     

Effect of adrenergic blocking drugs on secretion of luteinizing hormone in the ovariectomized ewe.

The effects of the adrenergic blocking drugs phenoxybenzamine, phentolamine, and pimozide on basal luteinizing hormone (LH) levels and on estrogen-induced LH release were tested in ovariectomized ewes. Phentolamine was given at a dose of 10 mg/kg; phenoxybenzamine was given at a dose of 8 mg/kg; and pimozide was given at a dose of 800 mcg/kg. Estradiol benzoate (EB) was given at a dose of 50 mcg/animal. Sera were assayed for LH levels by double-antibody radioimmunoassay. Phenoxybenzamine given as a single dose significantly reduced basal LH levels. Given at extremenly high doses, phenoxybenzamine was unable to consistently block estrogen-induced LH release. Pimozide significantly reduced basal LH levels in the ewes and blocked or greatly reduced estrogen-induced LH release in 9 of 10 treated animals. Reduced basal LH levels were seen with phentolamine injection but were of short duration of action. It is concluded that normal function of noradrenergic neurons is required for maintenance of normal basal LH release but unnecessary for estrogen-induced LH release. Dopaminergic neurons appear to facilitate basal and estrogen-induced LH release.     

Acute and chronic effects of oral enprostil, a synthetic dehydroprostaglandin E2, on uterine contractility

In acute experiments eleven nonpregnant women received a single oral dose of enprostil (prostaglandin E2 analogue) 35-140 mcg. Uterine activity was measured by a microtransducer-tipped Millar catheter. A single, oral dose of enprostil caused a long-lasting contracture response of the uterus. 3 h after enprostil, uterine resting pressure (RP) was still high. In chronic experiments, eleven women with regular menstrual cycles received 35 mcg or 70 mcg BID enprostil and placebo in a crossover, double-blind fashion from cycle day 10 +/- 3 for four weeks, then had a washout period of four weeks followed by another four-week treatment period. An increase of uterine RP after enprostil was dose-dependent. After two weeks of twice-daily administration of enprostil, the baseline RP was lower than after placebo (p less than 0.01) and the increase in RP after the morning enprostil less than that seen on the first day. In eight patients studied, the mean values of plasma progesterone were normal, both during placebo--and enprostil--treated cycles.     

Comparative clinical trial of vaccines against avian influenza

Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.     

Investigation of remaxol efficacy in complex therapy of experimental generalized tuberculosis on mice

Efficacy of remaxol in complex chemotherapy of generalized drug resistant tuberculosis was studied on mice. Mycobacterium tuberculosis 5419 SPBNIIF isolated from a patient with freshey diagnosticated pulmonary tuberculosis resistant to isoniazid (10 mcg/ml), rifampicin (40 mcg/ml), streptomycin (10 mcg/ml) and ethionamide (30 mcg/ml) was used in the experiments. The main polychemotherapy included 4 antituberculosis drugs in the highest therapeutic doses: isoniazid, amikacin, ethambutol and tavanic, the treatment course was 8 weeks. Remaxol was administered in a dose of 25 ml/kg intraperitoneally 5 times a week (14 injections). Significant activating effect of remaxol on the tension of the lung tissue local immunity was revealed by changes in the granuloma cell composition (from mainly epitheliod to mainly lymphoid) and by more frequent large lymphohistiocytic infiltrates. The use of remaxol also greatly increased the absorptive and digestive activity of the peritoneal macrophages phagocytosis, inhibited in the process of the experimental tuberculosis development.     

Haemonchus contortus: evaluation of two signal sequence trapping systems for detection of secreted molecules

Given that signal sequences between secreted proteins of different species can be interchanged, it is reasonable to expect that both mammalian and yeast signal sequence trapping (SST) systems would secrete Haemonchus contortus proteins with similar efficiency and quality. To determine if H. contortus cDNAs that contain a signal sequence could re-establish secretion of a reporter protein, mammalian and yeast SST vectors were designed, 10 H. contortus genes selected, and their respective cDNAs cloned into these two SST vectors. The selected molecules included genes known to code for excretory/secretory or membrane-bound proteins as potential test 'positives', and genes known to code for non-secreted proteins as test 'negatives'. While differentiation between secretion and non-secretion was evident in both systems, the results indicated greater efficiency was achieved when the mammalian system was used. Therefore, mammalian SST using COS cells would be a more useful tool to screen H. contortus cDNA libraries for potential secreted and type-1 integral membrane proteins than yeast SST.