Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies.

The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.

Spectroscopic investigations on the binding of an iodinated chlorin p6-copper complex to human serum albumin.

The insertion of suitable metals or high Z elements in tumour-avid tetrapyrrole compounds is a promising approach to obtain potential agents for multimodal cancer therapeutics and tumour imaging. Using chlorin p6, a chlorophyll derivative, we synthesized a novel iodinated chlorin p6-copper complex (ICp6-Cu) that can be applied to the photodynamic therapy and photon activation therapy of cancer. In the present study, we investigated the interaction of ICp6-Cu with human serum albumin (HSA) using UV-Vis absorption and fluorescence spectroscopy. The addition of HSA to ICp6-Cu at physiological pH led to a ∼7 nm red shift in its Soret and Q band absorption. The binding constant (Kb) and the number of binding sites (n) of ICp6-Cu obtained from the quenching of the intrinsic fluorescence of HSA were 2.9 × 106 M-1 and 1.2 respectively. The distance between the Trp-214 residue and ICp6-Cu computed from Förster non-radiative energy transfer (FRET) theory was 3.1 nm. The emission of the ICp6-Cu fluorescence when excited at the protein's Trp absorption (295 nm) further substantiated the FRET between the Trp residue and ICp6-Cu. Synchronous spectroscopy revealed that the quenching of protein Trp fluorescence was higher than that of Tyr with no significant shift in peak position. Results suggested that HSA acts as a carrier protein for ICp6-Cu with a high probability that the binding of ICp6-Cu occurred at subdomain IIA and the binding had no effect on the conformation of HSA.

Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-ß. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL.

Immunostimulatory potential and proteome profiling of Leishmania donovani soluble exogenous antigens.

Isolation of the soluble exogenous antigens (SEAgs), its immune response study and proteome profiling is an essential prerequisite for understanding the molecular pathogenesis of Leishmania donovani. The immunostimulatory potential of L. donovani SEAgs, purified from culture of L. donovani clinical isolate, was evaluated for their ability to induce cellular responses in treated/cured hamsters. SEAgs induced significant proliferative responses in lymphocytes (SI 5.6 ± 2.3; P < 0.01) isolated from cured hamster. In addition, significant NO production in response to SEAgs was also noticed in macrophages of hamsters, mouse and human cell lines (J774A-1 and THP1). Western blot analyses with antibodies against proteophosphoglycan (PPG; surface-expressed and secreted molecule) of L. donovani revealed that PPG molecules are also present in L. donovani SEAgs. Mass spectrometry (MS)-based proteome analysis of 12 protein bands of SEAgs through MALDI-TOF/TOF endorsed the identification of some Th1-stimulatory immunogenic proteins. These immunogenic proteins may offer increased hope for the discovery of new promising vaccine candidates against visceral leishmaniasis (VL). The overall results suggest that immunostimulatory molecules are present in the SEAgs, which may be further exploited, for developing a subunit vaccine against VL a fatal human disease.

Efficacy of Withania somnifera chemotypes NMITLI - 101R, 118R and Withaferin A against experimental visceral leishmaniasis.

The immunoprophylactic and therapeutic potentials of root extracts of Withania somnifera chemotypes (NMITLI-118, NMITLI-101) and pure withanolide-withaferin A was investigated against Leishmania donovani infection in hamsters. The naive animals, fed orally with immunostimulatory doses of chemotypes 101R, 118R (10 and 3 mg/kg) and withaferin A (9 and 3 mg/kg) for five consecutive days and challenged with Leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of parasite clearance, real-time analysis of mRNAs of Th1/Th2 cytokines (IFN-γ, IL-12, TNF-α, iNOS/IL-4, IL-10 and TGF-ß), NO production, reactive oxygen species (ROS) generation, lymphocyte transformation test and antibody responses. By day 45 p.c., there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α but decrease in IL-4, IL-10 and TGF-ß, an enhanced Leishmania-specific LTT response as well as ROS, NO and antileishmanial IgG2 levels in 101R-treated hamsters followed by 118R- and withaferin A-treated ones, respectively. When these chemotypes were given to L. donovani-infected hamsters at different doses, there was moderate therapeutic efficacy of chemotype 101R (~50%) at 30 mg/kg × 5 followed by the other two. The results established that the 101R is the most potential chemotype and can be evaluated for combination therapy along with available antileishmanials.

Reproductive preferences and contraceptive use: a comparison of monogamous and polygamous couples in northern Malawi.

There is now widespread agreement on the importance of men's role in reproductive decision-making. Several studies have argued that fertility preferences and their translation into behaviour differ between polygamous and monogamous unions. Studies investigating the dominance of men's preferences over women's preferences, in cases of couple disagreement, found mixed evidence of the effect of polygamy. However, an often cited limitation of these studies has been the inability to link husband's intention with each of his wives in a polygamous union. By adding fertility-intention questions to an on-going Demographic Surveillance Site in Karonga District in northern Malawi the fertility preferences and contraceptive use of husbands and wives were investigated. An analysis of the relationship between the level of agreement and disagreement between husbands' and wives' fertility preferences was then performed to gain insight into the reproductive decision-making process of polygamous couples.

Physicochemical and Biological Evaluation of Curdlan-Poly(Lactic-Co-Glycolic Acid) Nanoparticles as a Host-Directed Therapy Against Mycobacterium Tuberculosis.

Nanoparticles (NPs) that can activate macrophages infected with the tuberculosis causative pathogen Mycobacterium tuberculosis, could be an effective host directed therapy for the disease. In this study, curdlan was conjugated to poly(lactic-co-glycolic acid) (PLGA) to produce immunotherapeutic NPs. Various physicochemical characterizations were used to evaluate the curdlan-PLGA copolymer and the NPs. Molecular dynamics and simulation studies were used to characterize the interaction between curdlan, on the polymer and on NPs, with the Dectin-1 macrophage receptor. NPs with varying curdlan densities were evaluated for their effects on the production of pro- and anti-inflammatory cytokines in M. tuberculosis infected RAW264.7 macrophages. The killing efficacy of the NPs against intracellular M. tuberculosis was assessed. Physicochemical characterization of the curdlan-PLGA copolymer and NPs indicated successful formation of curdlan-PLGA copolymer and NPs of varying curdlan density (0-8% w/w) had sizes between 330 and 453 nm. Modelling studies showed curdlan to have a strong affinity for Dectin-1. Cytotoxicity assays showed the NPs to be non-toxic over 72 h. The proinflammatory cytokine TNF-α was found to be significantly upregulated by the NPs. The NPs reduced intracellular M. tuberculosis burden over 72 h. These NPs are a promising host directed therapy for intracellular eradication of M. tuberculosis.

Association of impaired cognitive functions with cardiovascular risk factors in elderly Indian population.

BACKGROUND: The prevalence of dementia is projected to rise dramatically in future with increasing life expectancy. Though dementia itself is not treatable in majority of cases, modification of co-morbid medical conditions may influence onset and rate of decline of cognitive functions. OBJECTIVE: To determine the prevalence of dementia in elderly by assessing cognitive function and to assess the association of cardiovascular risk factors with cognitive functions. STUDY DESIGN: Cross sectional analytical study. PARTICIPANTS: 400 consecutive elderly subjects > 65 years attending Geriatric OPD, Dept. of Medicine, Indira Gandhi Government Medical College, Nagpur, were recruited and assessed for cognitive functions by applying Mini Mental Status examination Score (MMSE). Relationships between cardiovascular risk factors and impaired cognitive score were determined. RESULTS: Prevalence of impaired cognitive function (MMSE Score < 25) was 33.25% (133 cases), while that of dementia (MMSE < 23) was 3.25 % (13 cases) in this elderly population. Impaired cognitive function was higher in those with low education and low socioeconomic status, (p = < 0.001). Increasing age, Female gender, alcohol intake and high cholesterol were found to be independently associated with impaired cognitive score in multiple logistic regression (p = < 0.001). Hypertension, diabetes mellitus, smoking and obesity were not associated with impaired cognitive score. CONCLUSION: Prevalence of cognitive impairment rises significantly as the age advances and is associated with alcohol intake and high cholesterol.

Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia.

Lonar lake, India: an impact crater in basalt.

Discovery of shock-metamorphosed material establishes the impact origin of Lonar Crater. Coarse breccia with shatter coning and microbreccia with moderately shocked fragments containing maskelynite were found in drill holes through the crater floor. Trenches on the rim yield strongly shocked fragments in which plagioclase has melted and vesiculated, and bombs and spherules of homogeneous rock melt. As the only known terrestrial impact crater in basalt, Lonar Crater provides unique opportunities for comparison with lunar craters. In particular, microbreccias and glass spherules from Lonar Crater have close analogs among the Apollo specimens.

Clinical profile of chikungunya fever in patients in a tertiary care centre in Maharashtra, India.

BACKGROUND & OBJECTIVE: In India a chikungunya fever outbreak started in December 2005 when the country experienced more than 13 lakhs of chikungunya infected cases. We undertook this study to study detailed clinical profile of chikungunya fever in both indoor and outdoor patients in a tertiary care hospital in Nagpur, Maharashtra in 2006. METHODS: Suspected cases of chikungunya fever (n=405) during the period of July to September 2006, having clinical triad of fever, arthralgia and/or rashes were included in the study. Clinical profile was studied in all the cases. Of the 405 samples collected, 166 were tested for serum CHIK IgM antibodies. RESULTS: Of the 166 samples tested for CHIKV IgM antibodies, 87 (52.4%) were positive (confirmed cases). Male: female ratio was 2.3:1. Fever and arthralgia were present in all cases. Rash was present in 27 (31%) confirmed and 38 (12%) suspected cases. Lymphadenopathy was present in 12 (13.8 %) confirmed and 4 of suspected cases. Chronic polyarthritis was seen in 22 (25.3%) confirmed and 75 (23.6%) suspected cases. Neurological manifestations were observed in 08 (9%) confirmed and 10 (3.14%) suspected cases. Mortality was 7 (2.2%) in 318 suspected cases and 3 (3.4%) in 87 confirmed cases. INTERPRETATION & CONCLUSION: Our findings showed that about half of the serum samples for CHIKV IgM antibody tested positive from cases suspected to have chikungunya fever. Fever, joint pain and headache were major symptoms. Certain rare manifestations like lymphodenopathy, oral ulcers and encephalitis were also seen. Mortality in confirmed cases was about 3.4 per cent.

Prophylactic efficacy of high-molecular-weight antigenic fractions of a recent clinical isolate of Leishmania donovani against visceral leishmaniasis.

T-cell mediated immune responses are key determinants to the natural course of infection caused by intracellular parasites such as Leishmania. Thus, T-cell activating proteins of these microbes continue to generate active interest particularly in view of their possible role in the design and development of newer and more effective vaccines. We have recently reported the presence of T-cell immunostimulatory antigens with the high-molecular-weight (MW) fractions (134-64.2 kDa) of whole Leishmania donovani antigen (strain 2001), which stimulated variable amounts of IFN-gamma, IL-12 and IL-10 in exposed immune individuals. The present study was undertaken to further evaluate these high-MW antigenic fractions (MW range >100-60 kDa) for potential protective efficacy. The high-MW region of the parasite was resolved into five antigenic fractions (Prep A-E) using continuous elution gel electrophoresis. Prior to in vivo protection studies in hamsters, these fractions were used to evaluate in vitro cellular responses in eight Leishmania-exposed individuals and treated cured hamsters. The protective efficacy of prep (A + B), C, D and E in combination with BCG was evaluated in inbred hamsters using standard immunization protocol. Proliferative responses were seen in all eight of eight exposed individuals to prep D [median stimulation index (SI): 5.2 (range 3.9-7.1)] and E [median SI: 5.6 (range 4.4-8.2)], five of eight individuals to prep B and prep C and three of eight to prep A [median SI: 0.2 (range 0.1-7.2)]. The median proliferative responses to prep D and prep E were significantly higher than to fraction prep A; (P < 0.05) but not to prep B and prep C. However, prep A-E induced equivalent levels of IFN-gamma, IL-10 and IL-12 cytokines. Fractions D and E also exhibited marked parasite inhibition in spleen (52.5% and 73.7%) and liver (65% and 80.2%) as compared with prep (A + B) (23% in spleen and 24% in liver) and prep C (38% in spleen and 24% in liver). Prep D and prep E vaccinated animals showed higher in vitro stimulatory responses (mean SI: 6.6 and 8.8) and nitric oxide (NO) induction (mean NO levels: 6.4 and 10.7 mug/ml) against whole cell extract as compared with other groups. The protection also correlated with presence of suppressed Leishmania-specific IgG levels in prep D and prep E immunized hamsters. These studies indicate the presence of immunostimulatory and protective molecules in 60-80 kDa region of L. donovani, which may be further exploited for developing a subunit vaccine.

Novel 3D ultrasound system for midline single-operator epidurals: a feasibility study on a porcine model.

BACKGROUND: We developed a real-time 3D ultrasound thick slice rendering technique and innovative Epiguide needle-guide as an adjunct to single-operator midline epidural needle insertions. Study goals were to determine feasibility of the technique in a porcine model and compare the visibility of standard and echogenic needles. METHODS: Thirty-four lumbar needle insertions were performed on six intact porcine spines ex vivo. Ultrasound scanning identified the insertion site and, using an Epiguide, the needle was guided into the epidural space through the ligamentum flavum in the midline plane, watched in real-time on the 3D ultrasound. Entry into the epidural space was judged by a loss-of-resistance technique. Needle visibility was rated by the anesthesiologist performing the technique using a 4-point scale; (0=cannot see, 1=poor, 2=satisfactory, 3=excellent), and later by an independent assessor viewing screenshots. The procedure was repeated at all lumbar levels using either the standard or echogenic needle. RESULTS: Successful loss-of-resistance to fluid was achieved in 76% of needle insertions; needle visibility with echogenic needles (94.2% rated satisfactory/excellent) was significantly better than with standard needles (29.4% satisfactory/excellent, P<0.0001). Successful loss-of-resistance was 93% when mean needle visibility was rated as 'excellent'. Inter-observer agreement between assessors was 'near-perfect' (weighted kappa=0.83). CONCLUSION: It is feasible to perform 3D ultrasound-guided real-time single-operator midline epidural insertions, in a porcine model. Echogenic needles were found to consistently improve needle visibility; and improved needle visibility tended to increase successful entry into epidural space.

Elf-1 is a transcriptional regulator of the Tie2 gene during vascular development.

Vascular development requires the tightly coordinated expression of several growth factors and their receptors. Among these are the Tie1 and Tie2 receptors, which are almost exclusively endothelial cell-specific. The critical transcriptional regulators of vascular-specific gene expression remain largely unknown. The Ets factors are a family of evolutionarily conserved transcription factors that regulate genes involved in cellular growth and differentiation. We have recently shown that the Ets factor NERF is a strong transactivator of the Tie1 and Tie2 genes. To extend these studies, we have begun to identify the Ets factors that are expressed in developing blood vessels of the chicken chorioallantoic membrane (CAM), a highly vascular embryonic network. RNA was extracted from microdissected CAM blood vessels, and reverse transcriptase-polymerase chain reaction was performed using oligonucleotides encoding conserved amino acids within the Ets domain. One of the polymerase chain reaction fragments was subcloned and identified as the chicken homologue of the Ets factor ELF-1, cELF-1. ELF-1 is most closely related to the Ets factor NERF. In situ hybridization and immunohistochemistry demonstrate that cELF-1 is enriched in developing chicken blood vessels. cELF-1 is also a strong transactivator of the Tie1 and Tie2 genes and can bind to conserved Ets sites within the promoters of these genes. A complex of similar size forms when gel shifts are performed with cellular extracts derived from the CAM blood vessels, which is recognized by an antibody against cELF-1. In summary, ELF-1 belongs to a subset of Ets factors that regulate vascular-specific gene expression during blood vessel development.

The occurrence of terminal ileal histological abnormalities in patients with coeliac disease.

INTRODUCTION: Coeliac disease causes histological changes throughout the small bowel, but is often a proximal lesion. We wanted to assess whether terminal ileal histological abnormalities occurred more commonly in patients with coeliac disease and if specific assessment of intraepithelial lymphocytes increases the recognition of undiagnosed coeliac disease. METHODS: Terminal ileal biopsies were prospectively examined over a 3-year period (April 2001-May 2004). Patients were included if they were found to have a synchronous duodenal biopsy that gave a new diagnosis of coeliac disease (n=20). Terminal ileal biopsies taken at colonoscopy during the same period were also examined from four groups of patients: coeliac disease established on a gluten-free diet but with persisting symptoms (n=25), inflammatory bowel disease (n=47), chronic diarrhoea (n=44) and polyp surveillance (n=47). All biopsies were graded according to the Marsh criteria and an intraepithelial lymphocytes count per 100 enterocytes was obtained. RESULTS: There was only one patient from all five groups who had villous atrophy of the terminal ileal. This patient had a new diagnosis of coeliac disease. The mean intraepithelial lymphocytes count in the coeliac disease group was 23.7 intraepithelial lymphocytes/100 enterocytes. This was significantly higher than the control groups: coeliac disease on a gluten-free diet=17.5 (p<0.012), inflammatory bowel disease=12.3 (p<0.0001), diarrhoea=12.6 (p<0.0001) and polyp=13.7 (p<0.0002). Validating terminal ileal villous intraepithelial lymphocytes counts as a test for coeliac disease using an intraepithelial lymphocytes/100 enterocytes of >25 gives a sensitivity of 45% and a specificity of 97.8%. CONCLUSION: Routinely quantifying terminal ileal intraepithelial lymphocytes may be of limited clinical value. However, subjective recognition of raised intraepithelial lymphocytes on a terminal ileal biopsy should alert the clinician to the possibility of coeliac disease.

Acyclic pyrazolo[3,4-d]pyrimidine nucleoside as potential leishmaniostatic agent.

A new synthesis of 6-amino-1-hydroxyethoxymethyl-4 (5H)-oxopyrazolo[3, 4-d]pyrimidine (4) has been mentioned. Compound 4 exhibited inhibition of amastigotes of Leishmania donovani to the extent of 89 % at 30 microg/mL, whereas iso-guanine analogue 5 had the inhibition only to the extent of 52.8% at 100 microg/mL in vitro. In hamster model the maximum inhibitory response for compound 4 against amastigotes multiplication was observed to be 94% at 50 mg/kg single dose for 5 consecutive days.

Binding of benzo(a)pyrene and dibenz(a,h)anthracene to the Ah receptor in mouse and rat hepatic cytosols.

Binding of the polycyclic aromatic hydrocarbon (PAH) carcinogens [3H]benzo(a)pyrene (BP) and [3H]dibenz(a,h)anthracene [DB(a,h)A] to components in rodent hepatic cytosols was characterized by sucrose density gradient centrifugation and by gel permeation chromatography on Sephacryl S-300. In hepatic cytosols from Sprague-Dawley rats, [3H]BP and [3H]DB(a,h)A bound to a component which sedimented at 8 to 9S under low-ionic-strength conditions, and had a Stokes' radius of 4.7 nm. The 8 to 9S component also bound [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and [3H]-3-methylcholanthrene (MC), two compounds previously established as Ah receptor ligands. In hepatic cytosols from C57BL/6J mice [a strain genetically "responsive" for induction of aryl hydrocarbon hydroxylase (AHH, cytochrome P1-450) by PAHs], [3H]DB(a,h)A bound to a component sedimenting at 8 to 9S which had a Stokes' radius of approximately 6 nm. The 8 to 9S component also bound [3H]TCDD and [3H]MC, but no direct binding of [3H]BP could be detected at 8 to 9S in hepatic cytosol from C57BL/6J mice, nor could specific [3H]BP binding to the 6 nm component be detected in C57BL/6J cytosol by Sephacryl S-300 chromatography. The 8 to 9S component was not detectable in hepatic cytosol from DBA/2J mice (genetically "nonresponsive" to AHH induction by PAHs) with [3H]BP or [3H]DB(a,h)A, nor with the previously established Ah receptor ligands [3H]TCDD or [3H]MC. In addition to binding to the 8 to 9S-6 nm component in C57BL/6J cytosols, [3H]BP, [3H]DB(a,h)A, and [3H]MC also bound extensively to a cytosolic component sedimenting at 4 to 5S with a Stokes' radius of approximately 3 nm. The 4 to 5S-3 nm component was present in hepatic cytosols from genetically nonresponsive DBA/2J mice, as well as in genetically responsive C57BL/6J mice. Binding of [3H]BP, [3H]DB(a,h)A, and [3H]MC to the 8 to 9S component in rodent hepatic cytosols was eliminated by incubation in the presence of a 100-fold molar excess of nonradioactive TCDD, whereas TCDD had no effect on binding of [3H]BP, [3H]DB(a,h)A, or [3H]MC to the 4 to 5S-3 nm component. The 8 to 9S component segregates with the Ahb allele in genetic crosses with mice, but the 4 to 5S component is not associated with the Ahb allele which governs AHH responsiveness. Specificity of chemicals that bind to the 8 to 9S component and segregation of the 8 to 9S component with the Ahb allele identify it as the Ah receptor which functions to regulate AHH induction in animals treated with PAHs.(ABSTRACT TRUNCATED AT 400 WORDS)

The leadership characteristics of the preceptor in selected clinical practice settings in Botswana.

A non-experimental, explorative, descriptive, quantitative study was undertaken. The purpose was to explore and describe the views of preceptors and preceptees regarding the fulfilment of the role of the preceptor in selected clinical nursing practice settings in the Botswana context. The study included 72 preceptors and 200 nursing students/preceptees who voluntary agreed voluntarily to participate in the study. A questionnaire was used to collect data, which was analyzed by using descriptive and inferential statistics. The findings of this study indicated that the preceptor lacked leadership characteristics in the accompaniment of the preceptee. These constraints included the lack of desirable characteristics such as intellectual, emotional, physical and other traits that are common to all good leaders. Recommendations were stated for improvements in selecting preceptors with certain leadership skills for the clinical practice settings. The limitations of this study were highlighted.

A randomized controlled trial comparing Ametop™ with placebo for reducing pain associated with local anesthetic skin infiltration before neuraxial anesthesia in parturients.

BACKGROUND: Between 10-22% of the general population experience needle phobia. Needle phobic parturients are at increased risk of adverse outcomes. We assessed the efficacy of topical Ametop™ (tetracaine 4%) gel in reducing the pain associated with local anesthetic skin infiltration before neuraxial block in non-laboring women. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Ametop™ or placebo was applied to the skin of the lower back at least 20min before neuraxial block using a standardized technique with 1% lidocaine skin infiltration. The primary outcome was numeric pain score (0-10) 30s after lidocaine infiltration. Groups were compared using Welch's t-test. RESULTS: Thirty-six subjects in each group were analyzed. There was a statistically significant difference in the mean (standard deviation) pain score between the Ametop™ and the placebo groups: 2.36±1.80 and 3.51±2.22, respectively (P=0.019). There were no significant adverse events. CONCLUSION: The mean numeric pain score in the Ametop™ group was 33% lower compared to the placebo group. Topical Ametop™ gel applied at least 20min before local anesthetic infiltration of the skin prior to neuraxial block in elective cesarean delivery may be a useful adjunct in needle phobic women.

Helium-neon laser preirradiation induces protection against UVC radiation in wild-type E. coli strain K12AB1157.

We have observed that preirradiation with a helium-neon laser (632.8 nm) induces protection against UVC radiation in wild-type E. coli strain K12AB1157. The magnitude of protection was found to depend on the helium-neon laser irradiance, exposure time, and period of incubation between helium-neon laser exposure and subsequent UVC irradiation. The optimum values for dose, irradiance and interval between the two exposures were found to be 7 kJ/m(2), 100 W/m(2) and 1 h, respectively. The possible involvement of singlet oxygen in the helium-neon laser-induced protection is also discussed.