Sexual exposure and sexual behaviour in the interval between gonorrhoea treatment and test of cure: a cross-sectional cohort study.

OBJECTIVES: We explored sexual contact in the interval between the treatment for gonorrhoea and attending for a test of cure (ToC) and identified factors associated with sexual contact in this period. METHODS: Multivariable analysis of demographic, behavioural and clinical data with self-reported sexual contact prior to attending for a gonorrhoea ToC evaluation among participants recruited into the 'Gentamicin for the Treatment of Gonorrhoea' trial in England, between October 2014 and November 2016. Associations with sexual contact were expressed as prevalence ratios (PR) and their corresponding 95% CI. RESULTS: The median time to ToC was 15 days (interquartile range 14-20 days). 197/540 (37%) participants reported sexual contact in the time between treatment and ToC. Of these, 173/197 (88%) participants reported inconsistent condom use, including with previous partners (133/197 (68%)). A history of gonorrhoea (adjusted PR (aPR) 1.32 (1.03 to 1.69)) or syphilis (aPR 1.19 (1.08 to 1.32)), being in regular (aPR 1.71 (1.41 to 2.09)) sexual relationships, high number of partners in the last 3 months (aPR 1.77 (1.25 to 2.51))-'more than 5 partners' vs '0 to 1 partner', and attending for a ToC more than 14 days after treatment (aPR 1.40 (1.08 to 1. 81)) were associated with reporting sexual contact before the ToC appointment. However, age (aPR (1.00 (0.99 to 1.01)) and presenting with specific symptoms at baseline (aPR 1.17 (0.95 to 1.44)) were not associated with sexual contact by the ToC attendance. CONCLUSION: Sexual activity after receiving treatment for gonorrhoea and prior to a ToC evaluation was common. This was associated with previous infection history and specific behavioural characteristics. Knowledge of these factors can help guide safe sex counselling at the time of treatment.

Time to resolution of genital symptoms for uncomplicated gonorrhoea: a prospective cohort study.

OBJECTIVES: To determine the time to resolution of symptoms (TTR) following treatment of uncomplicated gonorrhoea and to identify factors associated with TTR in a cohort of sexual health clinic attendees. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. We analysed demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria, who subsequently experienced microbiological clearance of Neisseria gonorrhoeae 2 weeks after treatment. Testing for gonorrhoea was performed using a nucleic acid amplification test. The results were expressed as median TTR (IQR) and HRs with 95% CIs for resolution of symptoms. RESULTS: 216 participants (89% male) with a mean age of 32 years reported genital discharge (204/216 (94%)) or dysuria (173/216 (80%)) at their baseline visit. Symptom resolution occurred in 202/216 (94%) at the 2-week follow-up appointment. The median TTR was 2 days (IQR 1-3 days). 50/216 (23%) patients presented with gonorrhoea-chlamydia coinfection at their baseline attendance and in this group symptom resolution was slower (3 days for gonorrhoea-chlamydia coinfection compared with 2 days for gonorrhoea only, HR 0.68 (95% CI 0.48 to 0.95)). TTR was also longer in women (4 days for females compared with 2 days for males, HR 0.47 (95% CI 0.29 to 0.77)). CONCLUSIONS: The time to resolution of genital symptoms following effective treatment of gonorrhoea is variable, but 90% of patients report symptom resolution within 1 week. Concurrent chlamydia infection and being female were associated with prolonged TTR.

Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae: data from GToG.

OBJECTIVES: Neisseria gonorrhoeae (NG) infection can resolve without antibiotic treatment, however the literature describing the frequency of clearance at individual sites, how rapidly it occurs and potential predictive factors is limited. In this analysis of a subpopulation identified from a large multicentre UK cohort, we describe the overall rate of spontaneous clearance of infection and explore factors associated with this. METHODS: Data from the Gentamicin compared with Ceftriaxone for the Treatment of Gonorrhoea randomised controlled trial consisting of 720 patients with NG were analysed. A subgroup of individuals had both a pretrial test sample and a trial enrolment sample taken. Those who had cleared NG between initial presentation and subsequent entry into the trial without antibiotic treatment were deemed to have spontaneously cleared. Sociodemographic characteristics, sexual history and sites of infection for those who spontaneously cleared infection were compared with that of those who did not. We also estimated the time interval to clearance. RESULTS: Overall, the proportion who had spontaneous clearance was 20.5% (83/405). Clearance of infection occurred over a median of 10 days (IQR 7-15 days). The cohort who spontaneously cleared were similar to those who did not in terms of age, gender, sexual orientation, HIV status and previous NG infection. Chlamydia coinfection was more frequent in the 'no spontaneous clearance group' (11.1% (9/83) cf 22.0% (69/322)) (p=0.029). Dysuria was reported more often in the 'no spontaneous clearance group' (4.8% (4/83) cf 13.0% (42/322)) (p=0.035). CONCLUSION: We present data from a large cohort of NG-infected individuals, of whom a significant proportion had spontaneous clearance of infection. This is consistent with previous smaller studies. If this is indicative of cure, point-of-care testing prior to treatment has the potential to reduce unnecessary exposure to antimicrobials. Further work to assess the importance of bacterial load, genotype and host immune response on spontaneous clearance of infection is required. TRIAL REGISTRATION NUMBER: ISRCTN51783227.

Factors associated with time to presentation for individuals with symptomatic uncomplicated genital gonorrhoea: a cross sectional cohort study of GToG trial participants.

OBJECTIVES: To determine the variation in the time from onset of symptoms to clinical presentation (time to presentation [TTP]) in a cohort of sexual health attendees with symptomatic uncomplicated genital gonorrhoea and to identify factors associated with TTP. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. Multivariable analysis was performed using prospectively collected demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria who tested positive for Neisseria gonorrhoeae using a nucleic acid amplification test. The results were expressed as geometric mean ratios (GMR) with 95% CI for time to presentation after onset of symptoms. RESULTS: 316 participants (269 men and 47 women) with a median age of 27.6 years (IQR 23.0-34.8) were included. 194 (61%) were Caucasian, 29 (9%) Black African, 27 (9%) Asian and 66 (21%) of other ethnicities. Median TTP was 3 days for men (IQR 2-7) and 14 days for women (IQR 7-21). Participants reported genital discharge (297/316 [94%]), dysuria (251/316 [79%]), both genital discharge and dysuria (232/316 [73%]) and other concurrent symptoms 76/316 (24%) (e.g., rectal bleeding or genital itching). 45/316 (14%) participants reported sexual contact while symptomatic, of whom TTP was more than 7 days in 32/45 (71%). A longer TTP was associated with gender (female cf. male, GMR 2.34 [1.67 to 3.26]), no prior history of gonorrhoea (GMR 1.46 [1.15 to 1.86]), 'regular' or 'ex-regular' sexual relationship (regular cf. one off GMR 1.35 [1.05 to 1.72]); ex-regular cf. one off GMR 1.88 [1.12 to 3.14]), and being heterosexual (GMR 1.69 [1.31 to 2.19]). CONCLUSION: Specific demographic and behavioural factors are associated with a longer TTP in individuals with symptomatic genital gonorrhoea. Detailed knowledge of these factors can be used to prioritise and optimise gonorrhoea management and prevention.

Factors associated with severity and resolution of intramuscular injection site pain following treatment for uncomplicated gonorrhoea: a prospective cohort study of GToG trial participants.

Background:Intramuscular injection (IMI) pain reduces the acceptability of treatment, but data identifying those at highest risk of severe pain following an injection are limited. This study identified factors associated with the severity, duration and resolution of IMI pain following treatment for uncomplicated gonorrhoea. Methods: Data from a subset of participants (aged 16-70 years) recruited between October 2014 and November 2016 into the 'Gentamicin for the treatment of gonorrhoea' trial in England were analysed. Pain was measured using a visual analogue scale (VAS) immediately after injection. Self-reported duration of pain was collected at a scheduled 2-week follow-up visit. Results: Overall, 688 participants (82% male), reported a median pain VAS score of 23.5 (range 0-100), which was moderate-severe (VAS score >30) in 38% (262/688) of participants. Age [adjusted odds ratio (aOR) 0.86 per 5-yearly increase, (0.78-0.94)], gender [female cf. male, aOR 1.62 (1.18-2.24)], ethnicity [Asian cf. Caucasian, aOR 2.79 (1.72-4.51)], body mass index [aOR 0.80 per 5 kgm-2 increase, (0.72-0.89)] and antibiotic regimen [gentamicin cf. ceftriaxone, aOR 3.92, (3.12-4.93)] were associated with moderate-severe injection pain. The median duration of pain was 2 h (range 0-648). Gender [female cf. male, adjusted hazard ratio (aHR) 0.76 (0.57-1.00)], ethnicity [Mixed race cf. Caucasian, aHR 0.64 (0.45-0.92)], self-reported pain [aHR 0.97 per 10 mm VAS score increase, (0.95-0.99)] and symptom status [asymptomatic cf. symptomatic aHR 1.35 (1.12-1.64)] were associated with pain resolution. Conclusions: IMI pain is influenced by specific demographic, anthropometric and clinical factors. Knowledge of these factors will help identify those most at risk of pain.

The association between symptom or microscopy based diagnosis of bacterial vaginosis (BV) and response to treatment in women with recurrent BV.

BACKGROUND: Bacterial vaginosis (BV) is a common condition, yet accurate diagnosis remains a challenge. We explored symptom and microscopy-based diagnosis of BV and assessed the influence of these diagnostic approaches on treatment response. METHODS: BV diagnosis based on patient-reported symptoms, and vaginal swab gram stain microscopy at local laboratories and a central laboratory were compared for women recruited into the VITA trial in England. Multivariable analysis was used to assess the association between the method of diagnosis and symptom resolution 2 weeks after metronidazole treatment. RESULTS: 517 women presenting with vaginal discharge (470/517 [91%]) and/or malodour (440/517 [85%]) were included. The accuracy of patients' vaginal symptoms compared to local laboratory microscopy for BV diagnosis were -discharge, sensitivity 90% and specificity 5%; malodour, sensitivity 84% and specificity 12%, and compared to a central laboratory diagnosis were -discharge, sensitivity 91% and specificity 8%; malodour, sensitivity 88% and specificity 18%. 143/204 (70%) participants reported symptom resolution after treatment and this was associated with a positive baseline local laboratory diagnosis (adjusted relative risk-aRR 1.64 [1.02 to 2.64]), but not with a positive central laboratory diagnosis (aRR 1.14 [0.95 to 1.37]). Symptom resolution occurred in 75% (83/111) of women who were symptom positive/central laboratory BV positive compared to 65% (58/89) who were symptom positive/microscopy negative. CONCLUSION: Symptoms correlated poorly with microscopy-based BV diagnosis but two-thirds of women with a symptom positive/microscopy negative diagnosis experienced symptom resolution following metronidazole treatment. Further studies are needed to determine the optimal investigation and treatment for microscopy-negative women with typical BV symptoms.

The frequency and duration of side-effects associated with the use of oral metronidazole; A prospective study of VITA trial participants.

BACKGROUND: The tolerability of metronidazole is often perceived as being poor and in particular as being a cause of gastrointestinal side effects, but the frequency, severity and duration of adverse effects (AE) is not well characterised. This study assessed the frequency and type of metronidazole associated AEs in women treated for bacterial vaginosis. METHODS: An exploratory study of participants from the lactic acid gel versus metronidazole for treating bacterial vaginosis (VITA) randomised controlled trial. In this sub-study, women aged ≥16 years, diagnosed with bacterial vaginosis and who received oral MTZ (400 mg twice daily, for 7 days) were followed up prospectively over 2 weeks. Baseline demographic and clinical data, and self-reported data on the incidence, time to onset, and duration of AEs were analysed. RESULTS: 155 women were included, of whom 64% (99/155) reported at least one metronidazole AE, including 47% (72/155) who reported gastrointestinal symptoms (nausea and/or vomiting [52/155], abdominal pain [31/154] or diarrhoea [31/154]) mostly within 3 days of starting treatment and resolving within 5 days of onset. Treatment discontinuation occurred in 8% (12/148) overall and AEs were given as the reason for discontinuing in only 3% (4/148). CONCLUSION: Overall, metronidazole side effects occurred commonly, but resolved within a few days and had a limited impact on treatment completion.

Economic evaluation of antimicrobial resistance in curable sexually transmitted infections; a systematic review and a case study.

OBJECTIVE: To provide a summary of the economic and methodological evidence on capturing antimicrobial resistance (AMR) associated costs for curable sexually transmitted infections (STIs). To explore approaches for incorporating the cost of AMR within an economic model evaluating different treatment strategies for gonorrhoea, as a case study. METHODS: A systematic review protocol was registered on PROSPERO (CRD42022298232). MEDLINE, EMBASE, CINAHL, Cochrane Library, International Health Technology Assessment Database, National Health Service Economic Evaluation Database, and EconLit databases were searched up to August 2022. Included studies were analysed, quality assessed and findings synthesised narratively. Additionally, an economic evaluation which incorporated AMR was undertaken using a decision tree model and primary data from a randomised clinical trial comparing gentamicin therapy with standard treatment (ceftriaxone). AMR was incorporated into the evaluation using three approaches-integrating the additional costs of treating resistant infections, conducting a threshold analysis, and accounting for the societal cost of resistance for the antibiotic consumed. RESULTS: Twelve studies were included in the systematic review with the majority focussed on AMR in gonorrhoea. The cost of ceftriaxone resistant gonorrhoea and the cost of ceftriaxone sparing strategies were significant and related to the direct medical costs from persistent gonorrhoea infections, sequelae of untreated infections, gonorrhoea attributable-HIV transmission and AMR testing. However, AMR definition, the collection and incorporation of AMR associated costs, and the perspectives adopted were inconsistent or limited. Using the review findings, different approaches were explored for incorporating AMR into an economic evaluation comparing gentamicin to ceftriaxone for gonorrhoea treatment. Although the initial analysis showed that ceftriaxone was the cheaper treatment, gentamicin became cost-neutral if the clinical efficacy of ceftriaxone reduced from 98% to 92%. By incorporating societal costs of antibiotic use, gentamicin became cost-neutral if the cost of ceftriaxone treatment increased from £4.60 to £8.44 per patient. CONCLUSIONS: Inclusion of AMR into economic evaluations may substantially influence estimates of cost-effectiveness and affect subsequent treatment recommendations for gonorrhoea and other STIs. However, robust data on the cost of AMR and a standardised approach for conducting economic evaluations for STI treatment which incorporate AMR are lacking, and requires further developmental research.

STI testing and subsequent clinic attendance amongst test negative asymptomatic users of an internet STI testing service; one-year retrospective study.

AIM: To explore the characteristics of online STI test users, and assess the frequency and factors associated with subsequent service use following a negative online STI test screen in individuals without symptoms. METHODS: One-year retrospective study of online and clinic STI testing within a large integrated sexual health service (Umbrella in Birmingham and Solihull, England) between January and December 2017. A multivariable analysis of sociodemographic and behavioural characteristics of patients was conducted. Sexual health clinic appointments occurring within 90 days of a negative STI test, in asymptomatic individuals who tested either online or in clinic were determined. Factors associated with online STI testing and subsequent clinic use were determined using generalized estimating equations and reported as odds ratios (OR) with corresponding 95% confidence intervals (CI). RESULTS: 31 847 online STI test requests and 40 059 clinic attendances incorporating STI testing were included. 79% (25020/31846) of online STI test users and 49% (19672/40059) of clinic STI test takers were asymptomatic. Online STI testing was less utilised (p<0.05) by men who have sex with men (MSM), non-Caucasians and those living in neighborhoods of greater deprivation. Subsequent clinic appointments within 90 days of an asymptomatic negative STI test occurred in 6.2% (484/7769) of the online testing group and 33% (4960/15238) for the clinic tested group. Re-attendance following online testing was associated with being MSM (aOR 2.55[1.58 to 4.09]-MSM vs Female) and a recent prior history of STI testing (aOR 5.65[4.30 to 7.43] 'clinic tested' vs 'No' recent testing history). CONCLUSIONS: Subsequent clinic attendance amongst online STI test service users with negative test results was infrequent, suggesting that their needs were being met without placing an additional burden on clinic based services. However, unequal use of online services by different patient groups suggests that optimised messaging and the development of online services in partnership with users are required to improve uptake.

An exploration of patient satisfaction with and experience of a sexual abuse survivors clinic.

BACKGROUND: The scale and extent of sexual violence perpetrated in the United Kingdom is being increasingly acknowledged. Support after the initial disclosure is often sought in NHS sexual health clinics. The purpose of this service evaluation was to explore patient satisfaction and experience amongst sexual health clinic attendees who disclosed sexual violence and were subsequently managed in a specialist sexual abuse survivors clinic. METHODS: Semi-structured interviews were conducted with ten service users and interview transcripts were analysed using interpretative phenomenological analysis (IPA) to assess users' experiences within the clinic. RESULTS: Participants were all female (aged 18-54 years) and had experienced sexual violence between 2 weeks and 15 years prior to interview, and the majority self-identified as White British (6/10). IPA analysis revealed three distinct overarching themes which were important to this group of patients when evaluating their care: delivery of care in the context of judgement and stigma, aspects of care identified as healing or harmful to recovery, and the importance of the processes of providing care. CONCLUSION: Understanding the experiences of sexual violence survivors in healthcare settings can optimise the provision of patient-oriented care and support. This includes ensuring the service user is in control of the consultation, the risks of re-traumatisation are minimised, and individuals receive relevant and accurate information but in a manageable volume and format.

The effect of intramuscular injection technique on injection associated pain; a systematic review and meta-analysis.

AIM: To review the effect of different intramuscular injection (IMI) techniques on injection associated pain, in adults. METHODS: The review protocol was registered on PROSPERO (CRD42019136097). MEDLINE, EMBASE, British Nursing Index and CINAHL were searched up to June 2020. Included studies were appraised and a meta-analysis, where appropriate, was conducted with a random effects model and test for heterogeneity. Standardised mean difference (SMD) with a 95% confidence interval in reported injection pain (intervention cf. control) was reported. RESULTS: 29 studies were included in the systematic review and 20 studies in the meta-analysis. 13 IMI techniques were identified. 10 studies applied local pressure to the injection site. Of these, applying manual pressure (4 studies, SMD = -0.85[-1.36,-0.33]) and Helfer (rhythmic) tapping (3 studies, SMD = -2.95[-5.51,-0.39]) to the injection site reduced injection pain, whereas the use of a plastic device to apply local pressure to the skin (ShotBlocker) did not significantly reduce pain (2 studies, SMD = -0.51[-1.58,0.56]). Acupressure techniques which mostly involved applying sustained pressure followed by intermittent pressure (tapping) to acupressure points local to the injection site reduced pain (4 studies: SMD = -1.62[-2.80,-0.44]), as did injections to the ventrogluteal site compared to the dorsogluteal site (2 studies, SMD = -0.43[-0.81,-0.06]). There was insufficient evidence on the benefits of the 'Z track technique' (2 studies, SMD = -0.20[-0.41,0.01]) and the cold needle technique (2 studies, SMD = -0.73[-1.83,0.37]) on injection pain. The effect of changing the needle after drawing up the injectate on injection pain was conflicting and warming the injectate did not reduce pain. Limitations included considerable heterogeneity, poor reporting of randomisation, and possible bias in outcome measures from unblinding of assessors or participants. CONCLUSIONS: Manual pressure or rhythmic tapping over the injection site and applying local pressure around the injection site reduced IMI pain. However, there was very high unexplained heterogeneity between studies and risk of significant bias within small studies.

Transglutaminase 2 maintains a colorectal cancer stem phenotype by regulating epithelial-mesenchymal transition.

Transglutaminase 2 (TG2), a multifunctional protein, is reported in regulating the cancer stem cell (CSC) phenotype in various cancers. Our previous work suggested the link between TG2 and Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC). Here we demonstrate the importance of TG2 in CSC development in human CRC cell lines HCT116 and SW620. CRC spheroid cells showed increased CSC characteristics over their monolayer cells with increased expression of CD44 and over expression of Oct3/4, Sox2 and Nanog. They also showed increased EMT and invasiveness, and enhanced expression of TG2. TG2 inhibition by its selective inhibitor 1-155 reduced both spheroid formation and invasive potential of the spheroid cells. ß-catenin, a mediator of stem cell maintenance, was overexpressed in the spheroid cells and could be attenuated by TG2 inhibition. Spheroid cells possessed increased angiogenesis stimulating ability via overexpression of Vascular Endothelial Growth Factor (VEGF). Increased VEGF was present in the culture media from spheroid cells when compared to monolayer cultures which could be reduced by selective inhibition by 1-155. Stemness and malignancy in the colorectal spheroid cells was associated with increased TG2, EMT, ß-catenin and VEGF. Here we demonstrate that inhibiting TG2 reduces both stemness and angiogenic stimulating activity in CRC.

Current perspectives of sickle cell disease in Nigeria: changing the narratives.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder characterized by clinical heterogeneity that may be influenced by environmental factors, ethnicity, race, social and economic factors as well as genetic and epigenetic factors. Areas covered: The present review was carried out to provide a comprehensive assessment of the current burden of SCD and treatments available for persons with SCD in Nigeria with the aim of identifying surveillance and treatment gaps, informing to guide the planning and implementation of better crisis prevention measures for SCD patients and set an agenda for new areas of SCD research in the country. This review assessed medical, biomedical and genetic studies on SCD patients in Nigeria and other endemic countries of the world. Expert opinion: Integration of hydroxyurea therapy into the management of SCD and surveillance via new-born screening (NBS) for early detection and management will improve the survival of persons with SCD in Nigeria. However, it will be important to carry out pilot studies, initiate strategic advocacy initiatives to educate the people about NBS benefits, develop collaborations between potential stakeholders and design sustainable financing scheme.

Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells.

Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT. TGFß1 expression in CRC cells, and its level in the cell medium and extracellular matrix was increased in primary tumour CRCs overexpressing TG2 and could regulate TG2 expression and EMT by both canonical (RKO) and non-canonical (RKO and SW480) signalling. TGFß1 regulation was not observed in the metastatic SW620 cell line, but TG2 knockdown or inhibition in SW620 reversed EMT. In SW620, TG2 expression and EMT was associated with increased presence of nuclear ß-catenin which could be mediated by association of TG2 with the Wnt signalling co-receptor LRP5. TG2 inhibition/knockdown increased interaction between ß-catenin and ubiquitin shown by co-immunoprecipitation, suggesting that TG2 could be important in ß-catenin regulation. ß-Catenin and TG2 was also upregulated in SW620 spheroid cells enriched with cancer stem cell marker CD44 and TG2 inhibition/knockdown reduced the spheroid forming potential of SW620 cells. Our data suggests that TG2 could hold both prognostic and therapeutic significance in colon cancer.

Neurobehavioural and neurotoxic effects of L-ascorbic acid and L-tryptophan in lead exposed rats.

BACKGROUND: Lead is an environmental toxicant, occupational and environmental exposures remain a serious problem in developing and industrializing countries. OBJECTIVE: This study is designed to investigate the effects of L-ascorbic acid and L-tryptophan on the neurotoxicity and neurobehavioural alterations in lead exposed male Sprague Dawley rats. METHODS: Experimental animals were exposed to oral doses of lead (Pb), L-ascorbic acid, and L-tryptophan at 75 mg/kg body weight, 40 mg/kg body weight, and 20 mg/kg body weight respectively, while control animals received 0.90% saline solution. Oral administration spanned for four weeks after which changes in neuro-behaviour, organ weight, blood deposition of Pb, brain serotonin, tryptophan and neuronal redox status were determined. Changes in organ weight, blood lead levels, neuro-behavioural characteristics, brain serotonin and tryptophan contents, and brain redox status were determined. RESULTS: The results indicated that Pb exposure increased blood lead, organ-weight index, and behavioural signs of anxiety and aggression. The sub-chronic exposure to Pb also decreased brain serotonin, while causing oxidative stress by decreasing reduced glutathione levels, antioxidant enzyme activity and increasing lipid peroxidation and brain protein contents. L-ascorbic acid attenuated both Pb induced neuronal oxidative stress, and abnormalities in behaviour. But L-tryptophan ameliorated Pb altered neurobehaviour with no significant effect on Pb induced oxidative stress in the brain. Co-administration of L-ascorbic acid and L-tryptophan on Pb exposed rats showed a reversal in all indices assessed towards the physiological state of control. CONCLUSION: This suggests that L-ascorbic and L-tryptophan can be used to compliment chelating therapy in lead neurotoxicity.

Influence of Vitamin C and Vitamin E on testicular zinc content and testicular toxicity in lead exposed albino rats.

BACKGROUND: Occupational and environmental exposures to lead remain a public health problem as lead alters physiological processes by inducing oxidative stress and mimicking divalent cations. This study was designed to investigate the effects of Vitamin C (VC) and Vitamin E (VE) on the reproductive function of lead exposed male rats. Experimental animals were exposed to oral doses of lead, VC and VE at 60 mg/kg body weight, 40 mg/kg body weight, and 150 mg/kg body weight respectively, while control animals received 0.9% saline solution. Oral administration spanned for six weeks after which changes in testicular redox status, lead deposition, testicular zinc content, serum androgen content, semen quality and testis histology were examined. RESULTS: There were significant (p < 0.05) increases in oxidative stress indices and testicular lead content. A significant (p < 0.05) depletion of zinc in the testis of lead exposed animals was also observed. Fluctuations were observed in androgen levels of lead treated animals with a significant increase (p < 0.05) in Serum follicle stimulating hormone (FSH) and testosterone (TT) content, while there was no significant change in luteinizing hormone (LH) content. Testicular tissue showed an alteration in its normal histology with degeneration of the seminiferous epithelium accompanied by a significant reduction (p < 0.05) in the number of luminal spermatozoa. A downgrade in the semen appearance and semen quality -sperm motility, morphology, and count was also observed after lead exposure. VC and VE treatment showed a significant (p < 0.05) reversal of the physiological alteration induced by lead. CONCLUSIONS: Lead exposure resulted in a decline in the reproductive function of male rats by inducing oxidative stress, inhibiting enzymes and depleting testicular zinc contents. However, results clearly showed that VC and VE attenuated the deleterious impact of lead on the reproductive system.