Validation of the Lead Care II System in Cape vultures (Gyps coprotheres) in comparison to ICP-MS using pure standards.

Lead toxicosis remains a concern in raptors, especially following feeding on carcasses sourced from hunting. Rapid diagnosis of lead exposure and easy field monitoring is desirable. The LeadCareII analytical system, validated for rapid diagnoses of lead toxicity in humans, has been described as a useful evaluation system in various species. For this study we attempt to validate the LeadCareII system in the Cape Vulture (CV) (Gyps coprotheres). Blood samples from CV housed under captive conditions and low background lead exposure, were pooled and spiked with known concentrations of a lead standard (0-60 µg/dL). Samples were analyzed by the LeadCareII system and by ICP-MS. The final results showed that despite good linearity the LeadCareII system underestimated lead concentrations by up to 50 %. While the results can be corrected by the derived equation, this is not supported due to the large underestimations evident. The reason for the underestimation is presently unknown.

Diagnosis and presenting features of autoimmune hepatitis at a central referral hospital in South Africa.

Introduction Autoimmune hepatitis (AIH) has scarcely been reported on in patients of black African descent. Similarly, few studies have focused on the relationship between AIH and Human-Immunodeficiency Virus (HIV) infection. Aim We aim to describe the presenting features of AIH from a single referral centre in a Sub-Sahara African setting. We also compare the presenting features of HIV-infected and HIV-uninfected patients. Methods This study was a retrospective chart review. Patients were included if they fulfilled criteria for the International AIH Group simplified score for probable or definite AIH, were 18 years or older at inclusion, and attended the adult Gastroenterology clinic at Inkosi Albert Luthuli Central Hospital (IALCH) for the period 1/1/2015 to 31/12/2020 on at least 2 occasions. Results Forty cases were included, of which 33 (82.5%) were female and 33 (82.5%) were black African. Median age at diagnosis was 26 years. A diagnosis of a coexistent autoimmune disease was made in 22.5% of patients, with Systemic Lupus Erythematosus (SLE) being the most common (12.5%). Sixteen patients were HIV-infected, all of whom were female (p =0.03), with a significantly older age of disease onset as compared to their HIV-uninfected counterparts (median age 38 vs 17.5 years, p <0.001). Conclusion AIH is a disease most commonly affecting young females. Female sex and older age of onset is associated with AIH in HIV-infected individuals.

Prevalence and predictors of severe Crohn's disease at a tertiary hospital in South Africa.

Background Predicting severe Crohn's disease (SCD) can assist in planning risk reduction therapy for SCD, thereby improving disease outcomes. Objective To determine the prevalence and predictors of SCD in a sample of South African patients. Methods This was a retrospective chart review of patients with Crohn's disease (CD) attending the Gastroenterology Unit at a tertiary hospital in Durban, South Africa. Demographic and clinical variables at diagnosis of CD were collected and analysed for statistical association with development of SCD (defined as the presence of >/= 1 of the following over the course of CD: complex perianal disease, colonic resection >/= 2 small bowel resections, a single small bowel resection > 50cm, or construction of a definitive stoma). The prognostic utility of statistically significant variables was investigated by establishing their sensitivity, specificity, and predictive values for SCD.  Results The study consisted of 93 patients. The rate of SCD was 64.5%, with 63.3 % of patients developing SCD within 1 year of CD diagnosis. Ileocolonic location (p = 0.046) and penetrating disease at initial diagnosis of CD (p = 0.021) were statistically associated with SCD. The sensitivity, specificity, positive predictive value, and negative predictive value of ileocolonic location for SCD was 72.7%, 47.4%, 66.7% and 54.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of penetrating disease for SCD was 85.7%, 41.7%, 30.0% and 91.0%. Conclusion Most patients with CD developed SCD within 1 year of their CD diagnosis. CD with a penetrating phenotype at diagnosis is a good predictor for the devleopment of SCD and should be further investigated.

Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Airborne bacteria in veterinary surgical theatres in South Africa.

The bioaerosol composition of the theatre environment plays a determining role in the development of surgical site infections (SSIs). It has been demonstrated that the concentration of viable airborne bacteria is influenced by the level of room occupancy, utilisation of surgical attire and importantly, proper ventilation systems, which are often lacking in the average veterinary facility. The aim of this study was to evaluate the airborne bacterial load encountered in non-environmentally controlled small animal veterinary theatres during routine surgical sterilisations, and to correlate these findings with the managerial practices at the facility. Four veterinary facilities with differing throughputs and managerial practices were recruited into the study. Blood agar settle plates, open from first incision to last suture, were used to quantify organisms that could settle in an incision. The 45 plates yielded 487 bacterial isolates (53 species). The Micrococcus (28.8%) and Staphylococcus (16.8%) genera were predominant. Of the isolates 61.8% were classified as human/small animal commensals and 37.2% belonged to species previously implicated in small animal SSIs. Specific trends were additionally evident in the bioaerosol loads. High room occupancy, lack of surgical attire and exposure to the outside environment were associated with higher bacterial counts. Accumulation from consecutive procedures was identified and linked to total occupancy time of the room. Current mitigation measures were not ideal to minimise the SSI risk. Routine, frequent and thorough cleaning in combination with surgical attire utilisation is recommended to reduce the bioburden for patient benefit.

Evaluation of the proper use of medication available over the counter by subsistence and emerging farmers in Mbombela Municipality, South Africa.

South Africa has two types of animal farming systems, being the commercial industry and subsistence farming in more rural areas, with commercial farmers having more access to veterinary services. To cater for the absence of sufficient veterinary service, the country allows farmers to access certain over the counter medications (stock remedies), as a way to assist them to farm sustainably and profitably. However, with any drug use, their true benefits are only realized following correct use. The aim of this study was to describe and assess the adequacy of the current use of veterinary drugs by rural-based farmers. A scheduled structured questionnaire with close-ended questions and direct observation was employed. The most important finding was the absence of proper training in the area, with 82.9% not receiving any training related to livestock production or use/handling of stock remedies, highlighting the urgent need for proper training. Of interest, a large proportion of the farmers (57.5%) left the care of their animals to herders. Concerns were also noted in the application of withholding periods, transport of medication, disposal of medication, calculation of drug doses, correct route of administration and carcass disposal with no difference in response between farmers receiving training and those who didn't. These finding not only indicates the importance of farmer training, but shows that for such training to be effective, information should not only cover farming activities but must include primary animal health care and an understanding of information contained in package leaflets. It would also be important to ensure that herdsmen are also included in such training initiatives as they are the primary careers of the animals.

Antivirals for the treatment of mild and moderate COVID-19 in South Africa.

While the majority of COVID-19 cases in South Africa (SA) are mild, patients with severe COVID-19 requiring hospitalisation present with significant morbidity and mortality and place a substantial burden on healthcare services. Given the low vaccine uptake in SA and other low- and middle-income countries in sub-Saharan Africa, the high prevalence of comorbidities and limited healthcare system capacity, evidence-based interventions that reduce the risk of severe disease and death should be considered for implementation. Several antiviral classes have been newly developed or repurposed to treat COVID-19 early after infection to retard progression to severe disease and reduce the risk of death, particularly in the elderly and/or in patients with comorbidities. COVID-19 antivirals such as remdesivir, nirmatrelvir/ ritonavir and molnupiravir are safe and cost-effective and have received either full approval or emergency use authorisation from regulators. Using a proposed test-and-treat strategy, judicious use of antivirals could be impactful.

Establishment of local wastewater-based surveillance programmes in response to the spread and infection of COVID-19 - case studies from South Africa, the Netherlands, Turkey and England.

The COVID-19 pandemic has resulted in over 340 million infection cases (as of 21 January 2022) and more than 5.57 million deaths globally. In reaction, science, technology and innovation communities across the globe have organised themselves to contribute to national responses to COVID-19 disease. A significant contribution has been from the establishment of wastewater-based epidemiological (WBE) surveillance interventions and programmes for monitoring the spread of COVID-19 in at least 55 countries. Here, we examine and share experiences and lessons learnt in establishing such surveillance programmes. We use case studies to highlight testing methods and logistics considerations associated in scaling the implementing of such programmes in South Africa, the Netherlands, Turkey and England. The four countries were selected to represent different regions of the world and the perspective based on the considerable progress made in establishing and implementing their national WBE programmes. The selected countries also represent different climatic zones, economies, and development stages, which influence the implementation of national programmes of this nature and magnitude. In addition, the four countries' programmes offer good experiences and lessons learnt since they are systematic, and cover extensive areas, disseminate knowledge locally and internationally and partnered with authorities (government). The programmes also strengthened working relations and partnerships between and among local and global organisations. This paper shares these experiences and lessons to encourage others in the water and public health sectors on the benefits and value of WBE in tackling SARS-CoV-2 and related future circumstances.

Adverse effects of heat stress during summer on broiler chickens production and antioxidant mitigating effects.

Broiler chicken meat is a good source of protein consumed universally, and is one of the most commonly farmed species in world. In addition to providing food, poultry non-edible byproducts also have value. A major advantage of broiler chicken production is their short production cycle, which results in a greater rate of production in comparison to other species. However, as with any production system, there are constraints in broiler production with one of the most pressing being energy requirements to keep the birds warm as chicks and cool later in the growth cycle, as a result of the cost needing mechanical heating and cooling. While this is feasible in more advanced economies, this is not readily affordable in developing economies. As a result, farmers rely on natural ventilation to cool the rearing houses, which generally becoming excessively warm with the resultant heat stress on the birds. Since little can be done without resorting to mechanical ventilation and cooling, exploring the use of other means to reduce heat stress is needed. For this review, we cover the various factors that induce heat stress, the physiological and behavioral responses of broiler chickens to heat stress. We also look at mitigating the adverse effect of heat stress through the use of antioxidants which possess either an anti-stress and/or antioxidant effects.

Verification of the folkloric and anecdotal antidiabetic effects of Hypoxis hemerocallidea (Fisch., C.A. Mey. & Avé-Lall) and isolated, ß-sitosterol using early-stage type II spontaneous diabetic mutant BKS-Leprdb mice.

BACKGROUND: Previous studies in our laboratory in ex vivo assays have demonstrated H. hemerocallidea extract as potential antidiabetic agent through increased insulin release from pancreatic beta cells. Thus, for this study the early stage type II spontaneous diabetic mutant mice model was used to evaluate and determine the degree of the antidiabetic efficacy of H. hemerocallidea. METHODS: Eight-weeks-old type II spontaneous pre-diabetic mutant BKS-Leprdb mice were fed with feed supplemented with either H. hemerocallidea extract, isolated compound (ß-sitosterol) or chlorpropamide (positive control) for 4 weeks. The haematological parameters, clinical chemistry, glucose tolerance, feed intake, faecal output and body weights were measured. RESULTS: The blood glucose concentrations of all the animals treated with plant extract, ß-sitosterol compound and non-treated pre-diabetic animals did not return to baseline levels. Only the ß-sitosterol treatment and positive control groups resulted in a respective small decrease of 5.8 and 5.2% in the mouse weights over the study period, with no significant changes (p > 0.05) in food intake. However, there was a general trend for decrease in faecal output for all the groups. Albumin, triglycerides, and total cholesterol levels in ß-sitosterol and chlorpropamide-treated animals were lower, relative to untreated-animals. Animals fed with plant extract showed large amounts of internal fat. There were no significant changes (p > 0.05) in total serum protein, globulin, alanine aminotransferase, alkaline phosphatase, urea nitrogen and creatinine attributed to administration of treatments. In all groups, some animals showed lesions associated with cardiac puncture. Few animals except animals treated with plant extract, showed presence of a left-ventricular hypertrophic cardiomyopathy. The liver and kidneys for all groups appeared macroscopically normal and the thymuses were small (±2 mg). There were pathological signs in some of the animals particularly in myocardial fibres, renal tubular, glomerular, hepatocyte granularity and pancreas islets. However, there was no significance trend between the groups. CONCLUSION: Based on the results, none of the treatments could be considered highly effective for the management of type II pre-diabetes as sole therapeutic intervention.

The efficacy of fluazuron in the management of blowfly strike in sheep.

The blowflies Lucilia spp. and Chryomya spp. feature prominently as a leading cause of myiasis and production losses in sheep in South Africa. With chemical means of preventing and treating blowfly strike being a common manner of control, new molecules or formulations effective against blowfly strike are needed as resistance becomes more of a problem. For this study we evaluated the potential of topical application of fluazuron on sheep as an additional means to control blowflies. When pure fluazuron was applied to raw meat at the recommended dose for cattle, significant effects on adult fly development were observed. However when applied topically to post-mortally collected sheep pelts at the same dose rate, no significant effects were observed on larval repellence or larval development with fly development progressing as expected. A subsequent pharmacokinetic study showed virtually no systemic absorption together with significant wool binding. Despite demonstrating that fluazuron was effective against blowfly larvae, wool binding of the molecule preclude its use.

A fourteen-year audit of surgery for inflammatory bowel disease at a tertiary colorectal unit.

BACKGROUND: In South Africa, inflammatory bowel disease (IBD) is increasing in frequency. The purpose of the study was to document our experience with the surgical management of patients with IBD and describe the cohort undergoing surgical management of IBD in a KwaZulu-Natal province tertiary state sector hospital. METHODS: Retrospective analysis of a database of patients undergoing surgery for IBD. Demographics, site and disease duration, surgical indications, management and outcome were analysed. RESULTS: Of 397 patients with IBD, 136 had Crohn's disease (CD) (African 13, Indian 78, Coloured 10 and White 35) and 261 had ulcerative colitis (UC) (African 67, Indian 158, Coloured 9 and White 27). Eighty-six of 136 patients with CD required surgical referral. Ileo-colonic CD was most common and non-stricturing/non-penetrating disease behaviour predominated. Seventy-four patients with CD underwent 76 abdominal surgical procedures with in-hospital mortality of 3.5% and a morbidity of 20.9%. Twenty patients required anorectal fistula procedures. Recurrence occurred in nine patients (10.5%) and malignant transformation was seen in three patients (2.2%). One hundred and sixty-three of the 261 patients with UC had pancolitis. Failed medical management was the most common indication for surgical referral. Fiftyone patients with UC had surgery, (age 44.5 [IQR 27-56] years). Forty-five patients underwent 63 abdominal surgical procedures with an overall mortality of 17.7% and a morbidity of 39.2%. Colorectal cancer was seen in 10 patients (3.8%). Laparoscopic procedures were undertaken in eight CD patients (10.8%) and 29 UC patients (39%). The median hospital stay was 7 days for both open and laparoscopic resection. CONCLUSION: IBD is not uncommon in African patients, with UC being more frequent than CD. Postoperative mortality and potential for malignant transformation are higher for UC.

Venous thromboembolic disease in adults admitted to hospital in a setting with a high burden of HIV and TB.

BACKGROUND: HIV and tuberculosis (TB) independently cause an increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE are scarce. The Wells' DVT and PE scores are widely used but their utility in these settings has not been reported on extensively. OBJECTIVES: To evaluate new onset VTE, compare clinical characteristics by HIV status, and the presence or absence of TB disease in our setting. We also calculate the Wells' score for all patients. METHODS: A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited into the study between September 2015 and May 2016. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells' score were collected. RESULTS: We recruited 100 patients. Most of the patients were HIV-infected (n=59), 39 had TB disease and 32 were HIV/TB co-infected. Most of the patients had DVT only (n=83); 11 had PE, and 6 had both DVT and PE. More than a third of patients on antiretroviral treatment (ART) (43%; n=18/42) were on treatment for <6 months. Half of the patients (51%; n=20/39) were on TB treatment for <1 month. The median (interquartile range (IQR)) DVT and PE Wells' score in all sub-groups was 3.0 (1.0 - 4.0) and 3.0 (2.5 - 4.5), respectively. CONCLUSION: HIV/TB co-infection appears to confer a risk for VTE, especially early after initiation of ART and/or TB treatment, and therefore requires careful monitoring for VTE and early initiation of thrombo-prophylaxis.

Short communication: Characterization of an atypical maltose-negative Staphylococcus aureus through the use of phenotypic and molecular techniques.

The most clinically relevant staphylococci in veterinary medicine are those that are coagulase-positive, namely Staphylococcus aureus. During microbiological udder health monitoring (2009-2018), a new S. aureus strain (coagulase-positive and maltose-negative) was discovered as an emerging udder pathogen during routine examinations of South African dairy herds. This study challenged the conventional microbiological diagnosis of staphylococci by comparing its results to those of the MALDI-TOF mass spectrometry and 16S rRNA sequencing. Both of these tests confirmed that the maltose-negative staphylococcus (MNS), identified as Staphylococcus pseudintermedius by conventional microbiology, was S. aureus ST2992. Multi locus sequence typing was performed on 3 of the MNS isolates and indicated that these isolates were of single origin. These strains tested positive for both MALA and MALR genes (control: S. aureus ATCC 25923). Although the α-glucosidase gene was present, it was not expressed phenotypically. The latter may be attributed to the abnormal stop codon identified in the MALA gene sequence of S. aureus ST2992 (GenBank accession number, MN531305). The newly identified MNS has a field behavior different to that of maltose-positive S. aureus, and more similar to the low virulence of non-aureus staphylococci.

Pharmacokinetics of voriconazole after a single intramuscular injection in large falcons (Falco spp.).

Voriconazole is one of the main azoles used to treat invasive aspergillosis in falconry raptors and birds. Despite the fact that there are studies for oral and intravenous use of voriconazole in birds, there are none for its effect after intramuscular use. Empirical use of intramuscular voriconazole in falcons, indicated quicker therapy response than the oral one. Aim of this study is to evaluate the in vivo pharmacokinetic disposition of injectable voriconazole after a single intramuscular injection in large falcons (i.e., Gyrfalcons, Saker falcons, Peregrine falcons). No clinical side effects were observed in the falcons. Absorption of voriconazole was rapid (0.5-2 hours) and reached a plasma level (>1 µg/ml) which is above the minimal inhibitory concentration (MIC) for all known Aspergillus strains. This level was maintained for 16 to 20 hours, thus indicating that a single injection of 12.5 mg/kg is not enough if T > MIC is taken into consideration. On a newer aspect, according to the AUC24 unbound: MIC parameter would be indicated that this dose would be rather sufficient for most Aspergillus strains.

Ultrastructure changes induced by the phloroglucinol derivative agrimol G isolated from Leucosidea sericea in Haemonchus contortus.

Plant extracts used for the treatment of helminth infections in sheep are an alternative to chemical anthelmintic drugs. Previous studies have reported the anthelmintic activity of acetone leaf extracts of Leucosidea sericea. For this study, we evaluate the ultrastructure changes induced by the acetone leaf extract of L. sericea and the component agrimol G (AG) that was isolated for the first time on adult haemonchus parasites. Adult haemonchus parasites harvested from sheep were incubated with the plant extract and AG for 3 h and evaluated by both scanning and transmission electron microscopy in comparison and in combination with albendazole or ivermectin. In all cases the method of evaluation shows ultrastructural changes, with albendazole inducing mitochondrial damage and ivermectin inducing muscle degeneration, both as previously described. Incubation with the plant extract and AG resulted in the formation of numerous non-membrane bound multi-vesicular like bodies and evenly spread disruptions/erosion in the epicuticle. Combining AG with ivermectin or albendazole resulted in an absence of effect of AG. Based on the structural changes induced by AG, together with the absence of an effect in combination with ivermectin and albendazole would suggest a disrupted microtubular network. The latter does however require biochemical confirmation.

A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros.

The alleviation of pain and prevention of suffering are key aspects of animal welfare. Unfortunately, analgesic drugs are not available for all species. White rhinoceros (Ceratotherium simum), representing one of such species, which survive poaching attempts inflicted with severe facial injuries and gunshot wounds, nonetheless require analgesic support. To improve treatment conditions, this study explored the use of carprofen for the treatment of pain and inflammation in white rhinoceros. The pharmacokinetics of 1 mg/kg intramuscular carprofen was evaluated in six healthy white rhinoceros. The half-life of λz and mean residence time was 105.71 ± 15.67 and 155.01 ± 22.46 hr, respectively. The area under the curve and the maximum carprofen concentration were 904.61 ± 110.78 µg ml-1  hr-1 and 5.77 ± 0.63 µg/ml, respectively. Plasma TXB2 inhibition demonstrated anti-inflammatory properties and indicated that carprofen may be effective for a minimum of 48 hr in most animals. With its long half-life further indicating that a single dose could be effective for several days, we suggest that carprofen may be a useful drug for the treatment of white rhinoceros.

The use of toxicokinetics and exposure studies to show that carprofen in cattle tissue could lead to secondary toxicity and death in wild vultures.

Veterinary medicines can be extremely damaging to the environment, as seen with the catastrophic declines in Gyps vulture in South Asia due to their secondary exposure to diclofenac in their primary food source. Not surprisingly, concern has been raised over other similar drugs. In this study, we evaluate the toxicity of carprofen to the Gyps vulture clade through plasma pharmacokinetics evaluations in Bos taurus cattle (their food source) and Gyps africanus (a validated model species); tissue residues in cattle; and the effect of carprofen as a secondary toxicant as both tissue-bound residue or pure drug at levels expected in cattle tissues. Carprofen residues were highest in cattle kidney (7.72 ± 2.38 mg/kg) and injection site muscle (289.05 ± 98.96 mg/kg of dimension of 5 × 5 × 5 cm). Vultures exposed to carprofen as residues in the kidney tissue or pure drug equivalents showed no toxic signs. When exposed to average injection site concentrations (64 mg/kg) one of two birds died with evidence of severe renal and liver damage. Toxicokinetic analysis revealed a prolonged drug half-life of 37.75 h in the dead bird as opposed to 13.99 ± 5.61 h from healthy birds dosed intravenously at 5 mg/kg. While carprofen may generally be harmless to Gyps vultures, its high levels at the injection site in treated cattle can result in lethal exposure in foraging vultures, due to relative small area of tissue it is found therein. We thus suggest that carprofen not be used in domesticated ungulates in areas where carcasses are accessible or provided to vultures at supplementary feeding sites.

Chronic light exposure alters serotonergic and orexinergic systems in the rat brain and reverses maternal separation-induced increase in orexin receptors in the prefrontal cortex.

Maternal separation (MS) is a well-established rodent model of depression. Chronic constant light (CCL) treatment during adolescence has been shown to reverse the depression-like behaviour induced by MS. We aimed to further delineate the antidepressant effect of light by investigating the involvement of the dopaminergic, serotonergic and orexinergic systems. MS was used to induce changes in adult male Sprague-Dawley rats, some of whom were also treated with CCL for 3 weeks during adolescence. At P80, rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated dopamine release in the nucleus accumbens (NAc) using an in vitro superfusion technique. Enzyme-linked immunosorbent assays were employed to measure 5-hydroxytryptamine (5-HT) levels in the hypothalamus and prefrontal cortex (PFC). Western blotting was used to measure orexin receptor 1 (OXR-1) and 2 (OXR-2) in the PFC. MS did not affect 5-HT levels in these rats. However, CCL increased hypothalamic 5-HT and reduced 5-HT levels in the PFC. CCL had opposite effects on OXR levels in the PFC of maternally separated and non-separated rats. MS increased OXR-1 and OXR-2 levels in the PFC, an effect that was normalized by CCL treatment. MS reduced glutamate-stimulated dopamine release in the NAc, an effect that was not reversed by CCL. The present results suggest that CCL treatment affects 5-HT and orexinergic systems in the MS model while not affecting the MS-induced decrease in dopamine release in the NAc. The reversal of changes in the orexinergic system may be of particular relevance to the antidepressant effect of CCL in depression.

Gastrointestinal common variable immunodeficiency presenting with symptomatic hypocalcaemia ­ a case report

Common variable immunodeficiency (CVID) is a rare form of severe immunodeficiency manifested by recurrent bacterial infections with several gastrointestinal manifestations. Herein we describe an unusual presentation of CVID