Assessment of Fasciola and Paramphistomes co-infection in large ruminants through faecal egg counts around Taiping, Malaysia.

Emerging cases of Fasciola and Paramphistomes co-infection have been reported, especially in tropical regions. Thisis due to Fasciola and Paramphistomes sharing biological factors which influence the pattern of transmission, especially in faecal egg shedding due to interaction and competition in the definitive host. Most reports surveyed the occurrence of fasciolosis in ruminants with a lack of observation of faecal egg distribution. Therefore, present study is aimed to assess the distribution of Fasciola and Paramphistomes faecal egg count (fec) in co-infected large ruminants in Larut, Matang, and Selama areas (Taiping). A total of 371 faecal samples were collected at random from 23 ruminant herds. Flukefinder® sedimentation was used to quantify the Fasciola and Paramphistomes eggs. Descriptive analyses were performed to determine the prevalence of co-infections, and Spearman correlation analysis was used to correlate the fec. Overall, the prevalence of Fasciola and Paramphistomes co-infection was 23.7% (n=89/371) in Taiping. Prevalence of paramphistomosis was always higher than fasciolosis in overall and single infection, with 46.9% (n=174/371) and 22.9% (n=85/371) compared to 36.9% (n=137/371) and 12.9% (n=48/371) respectively. Egg per gram (epg) of both parasites were positively skewed with a median of 1.5 epg in fasciolosis and 10.5 epg in paramphistomosis. Spearman correlation analysis of the epg in co-infected bovine was found to have a moderately positive correlation with rs=0.39 (p-value<0.01). The recent study observed a moderate prevalence of Fasciola and Paramphistomes coinfection in a large ruminant population from Taiping, with the prevalence of paramphistomosis being higher than fasciolosis. Hence, this suggests that infection with one of these parasites increases the chance of infection with another. There is a need to integrate fec in parasite surveillance to monitor the trend of parasite transmission. Findings in the present study could tailor control strategies, especially for fasciolosis to limit the economic loss and prevent zoonotic transmission.

Assessment of Fasciola and Paramphistomes co-infection in large ruminants through faecal egg counts around Taiping, Malaysia

@#Emerging cases of Fasciola and Paramphistomes co-infection have been reported, especially in tropical regions. Thisis due to Fasciola and Paramphistomes sharing biological factors which influence the pattern of transmission, especially in faecal egg shedding due to interaction and competition in the definitive host. Most reports surveyed the occurrence of fasciolosis in ruminants with a lack of observation of faecal egg distribution. Therefore, present study is aimed to assess the distribution of Fasciola and Paramphistomes faecal egg count (fec) in co-infected large ruminants in Larut, Matang, and Selama areas (Taiping). A total of 371 faecal samples were collected at random from 23 ruminant herds. Flukefinder® sedimentation was used to quantify the Fasciola and Paramphistomes eggs. Descriptive analyses were performed to determine the prevalence of co-infections, and Spearman correlation analysis was used to correlate the fec. Overall, the prevalence of Fasciola and Paramphistomes co-infection was 23.7% (n=89/371) in Taiping. Prevalence of paramphistomosis was always higher than fasciolosis in overall and single infection, with 46.9% (n=174/371) and 22.9% (n=85/371) compared to 36.9% (n=137/371) and 12.9% (n=48/371) respectively. Egg per gram (epg) of both parasites were positively skewed with a median of 1.5 epg in fasciolosis and 10.5 epg in paramphistomosis. Spearman correlation analysis of the epg in co-infected bovine was found to have a moderately positive correlation with rs=0.39 (p-value<0.01). The recent study observed a moderate prevalence of Fasciola and Paramphistomes coinfection in a large ruminant population from Taiping, with the prevalence of paramphistomosis being higher than fasciolosis. Hence, this suggests that infection with one of these parasites increases the chance of infection with another. There is a need to integrate fec in parasite surveillance to monitor the trend of parasite transmission. Findings in the present study could tailor control strategies, especially for fasciolosis to limit the economic loss and prevent zoonotic transmission.

Case Report: Severe Hypernatremia From Ingestion of One's Own Urine.

An often unrecognized cause of hypernatremia is the ingestion of fluids or substances with high osmolality. We hereby report a case of severe hypernatremia with acute kidney injury in a severely debilitated patient with acute gouty arthritis who resorted to ingesting his own urine. Hypernatremia induced by drinking urine could be attributed to many underlying mechanisms, one of the important possible causes is the resultant high serum urea that leads to significant osmotic diuresis and a further increase in free water clearance. To the best of our knowledge this is the first case report that describes this unique cause of hypernatremia.

Identification of warning signs in Malaysian patients having COVID-19 infection who progress to severe form of the illness.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus, now widely known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused 3 major pandemic waves in Malaysia. We aimed to identify the warning signs as indicators that predict the progression of disease. MATERIALS AND METHODS: This is a retrospective cohort study of adult patients more than 12 years of age presenting with laboratory-confirmed COVID-19 admitted in three separate hospitals around the country. RESULTS: Of the 228 patients initially admitted with mild illness, 47 had progressed requiring oxygen. The median time from admission to deterioration was 3 days (IQR 2 - 5). Age more than ≥50years old (median age = 42.5, IQR = 28.8 - 57.0), higher temperature (mean = 37.3, IQR 36.8 - 38.0), MEWS score >3 (9, 19.1%), Neutrophil-to-lymphocyte ratio (NLR) >3.13 , (18, 38.3%) C-reactive protein (CRP) >5. (12, 27.3%), multiple zonal involvement on the chest radiography on admission (2, IQR 1-3) were more common in the deteriorated group on admission. On multivariate analysis, multiple comorbidities (HR = 7.40, 95 percent CI 2.58-21.2, p0.001), presence of persistent fever (HR = 2.88, 95 percent CI 1.15 - 7.2, p = 0.024), MEWS scoring >3 (HR of 6.72 ;95 percent CI 2.81-16.0, p0.001) were associated with progression to severe illness. CONCLUSION: In our cohort, we found that several factors were associated with the severity of COVID19. Early detection of these factors could correctly identify patients who need more intensive monitoring, and early referral for ICU care.

Comparison of transepidermal water loss and skin hydration in diabetics and nondiabetics.

BACKGROUND: Pruritus is common in patients with diabetes mellitus (DM), and may lead to complex dermatological conditions if left untreated. Pruritus can be caused by increased transepidermal water loss (TEWL) and reduced skin hydration. AIMS: To compare TEWL and skin hydration in patients with DM and controls, and to investigate associations between TEWL and skin hydration with glycated haemoglobin (HbA1c), fasting blood sugar (FBS), treatment, peripheral neuropathy (PN) and age in patients with diabetes. METHODS: This was a prospective, case-control study carried out at a tertiary medical centre in Kuala Lumpur, Malaysia. TEWL and skin hydration measurements were taken at six different body sites in both groups. RESULTS: In total, 146 patients (73 cases, 73 controls) were included (24 men and 49 women in each group). No significant difference in TEWL or skin hydration was seen between patients with DM and controls, but there were significant reductions in skin hydration in patients with DM who had FBS > 7 mmol/L (P < 0.01) or PN (P < 0.01). There was a reduction in TEWL over the anterior shin in patients with HbA1c levels > 6.5% (P < 0.02) and an increase in TEWL on the flank in patients on insulin injections at doses of > 1 U/kg/day (P < 0.01). In participants > 45 years old, there was a significant reduction in TEWL (P = 0.04) and hydration (P < 0.04) in the DM and control groups, respectively. CONCLUSION: There was no difference in TEWL and skin hydration in patients with DM compared with controls. In the DM group, reduction in skin hydration was associated with uncontrolled FBS and PN but not with HbA1c or DM treatment, whereas TEWL was lower in patients with FBS > 8 mmol/L and increased in patients with higher insulin requirement.

Switching from sulphonylurea to a sodium-glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia.

The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12-week, randomized, open-label, two-arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group.

The influence of fasting insulin level in post-gestational diabetes mellitus women receiving low-glycaemic-index diets.

Post-gestational diabetes mellitus (GDM) women are recommended weight loss to manage increased cardio-metabolic risks. We investigated the effects of lowering diet glycaemic index (GI) on fasting blood glucose (FBG), serum lipids, body weight and composition of post-GDM women with varying fasting insulin levels (INS). Seventy-seven Asian, non-diabetic women with previous GDM (aged 20-40 years, mean BMI: 26.4±4.6 kg m(-2)) were recruited. At baseline, 20 subjects with INS <2 µIU ml(-1) and 18 with INS 2 µIU ml(-1) received conventional dietary recommendations (CHDR) only. CHDR emphasised energy and fat intake restriction and encouraged increase in dietary fibre intakes. Twenty-four subjects with INS <2 µIU ml(-1) and 15 with INS 2 µIU ml(-1), in addition to CHDR, received low-GI education (LGI). Changes in FBG, serum lipids, body weight and body composition were evaluated. Subjects with INS <2 µIU ml(-1) had similar outcomes with both diets. After 1 year, subjects with INS 2 µIU ml(-1) who received LGI education had reductions in FBG and triglycerides. Subjects who received CHDR observed increase in both FBG and triglycerides (P<0.05). Among all subjects, diet GI was lower and dietary fibre intakes were higher in LGI compared with CHDR subjects (all P<0.05). Thus, in Asian post-GDM women with normal/higher INS, adding low-GI education to CHDR improved management of FBG and triglycerides.

Medical nutrition therapy administered by a dietitian yields favourable diabetes outcomes in individual with type 2 diabetes mellitus.

AIM: This prospective, single-group, pre-post design trial was conducted to evaluate the effect of individualised Medical Nutrition Therapy intervention administered by a dietitian in individuals with type 2 diabetes mellitus on glycaemic control, metabolic parameters and dietary intake. METHODS: Subjects (n=104; age=56.4 ±9.9 years; 37% male; years of diagnosis = 6.3 ±4.9 years) treated with diet and on a stabile dose of oral anti-diabetic agents were given dietary advice by a dietitian for a 12 week period. Individualised dietary advice was based on Malaysian Medical Nutrition Therapy for adults with type 2 diabetes mellitus. The primary outcome measure was glycaemic control (fructosamine and HbA1c level) and the secondary outcome included measures of anthropometry, blood pressure, lipid profile, insulin levels dietary intake and knowledge on nutrition. RESULTS: At week 12, 100 subjects completed the study with a dropout rate of 3.8%. The post-Medical Nutrition Therapy results showed a significant reduction of fructosamine (311.5 ±50 to 297 ±44 umol/L; P< 0.001) and HbA1c (7.6 ±1.2 to 7.2 +1.1%, p<0.001) with pronounced reduction for subjects who had very high HbA1c levels of >9.3% at baseline. Waist circumference (90.7 ±10.2 to 89.1 ±9.8 cm, p<0.05), HDL-cholesterol (1.1 ±0.3 to 1.2 ±0.3 mmol/L, p<0.05), dietary intake and nutrition knowledge score (42 ±19 vs. 75 ±17%; p< 0.001) were significantly improved from the baseline. CONCLUSIONS: Individualised Medical Nutrition Therapy administered by a dietitian resulted in favourable diabetes outcomes, which were more apparent for individuals with higher than optimal HbA1c levels at the start of the study.

Prevalence of diabetes in Malaysia and usefulness of HbA1c as a diagnostic criterion.

AIM: The prevalence of diabetes mellitus among Malaysians aged ≥ 30 years of age has increased by more than twofold over a 20-year period. This study aimed to determine the current status and to evaluate the diagnostic usefulness of the HbA(1c) cut-off point of 48 mmol/mol (6.5%). METHODS: Using a two-stage stratified sampling design, participants aged ≥ 18 years were recruited from five zones selected to represent Malaysia. An oral glucose tolerance test was performed on all those not known to have diabetes. RESULTS: A total of 4341 subjects were recruited. By World Health Organization criteria, the prevalence of diabetes mellitus was 22.9%; of that percentage, 10.8% was known diabetes and 12.1% was newly diagnosed diabetes. Diabetes was most prevalent amongst Indians (37.9%) and Malays (23.8%). Prevalence of new diabetes mellitus was only 5.5% (95% CI 4.9-6.3) when based on the HbA(1c) diagnostic criteria of 48 mmol/mol (6.5%) and, although the cut-off point was highly specific (98.1%), it was less sensitive (36.7%) compared with 45 mmol/mol (6.3%), which showed the optimal sum of sensitivity (42.5%) and specificity (97.4%) in identifying new diabetes mellitus. CONCLUSION: This study recorded an overall diabetes prevalence of 22.6%, almost a twofold increase from 11.6% reported in 2006. This was likely attributable to the higher prevalence of new diabetes (12.1%) diagnosed following an oral glucose tolerance test. An HbA(1c) of 45 mmol/mol (6.3%) was found to be a better predictive cut-off point for detecting new diabetes in our multi-ethnic population.

Predictors of ischaemic heart disease in a Malaysian population with the metabolic syndrome.

AIMS: Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these. METHODS: For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined. RESULTS: The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 µg/mmol creatinine for men, 3.5 µg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P < 0.001. The presence of an elevated albumin:creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P < 0.001). CONCLUSIONS: We confirmed the high prevalence of the metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality.

Human behavior state profile mapping based on recalibrated speech affective space model.

People typically associate health with only physical health. However, health is also interconnected to mental and emotional health. People who are emotionally healthy are in control of their behaviors and experience better quality of life. Hence, understanding human behavior is very important in ensuring the complete understanding of one's holistic health. In this paper, we attempt to map human behavior state (HBS) profiles onto recalibrated speech affective space model (rSASM). Such an approach is derived from hypotheses that: 1) Behavior is influenced by emotion, 2) Emotion can be quantified through speech, 3) Emotion is dynamic and changes over time and 4) the emotion conveyance is conditioned by culture. Empirical results illustrated that the proposed approach can complement other types of behavior analysis in such a way that it offers more explanatory components from the perspective of emotion primitives (valence and arousal). Four different driving HBS; namely: distracted, laughing, sleepy and normal are profiled onto the rSASM to visualize the correlation between HBS and emotion. This approach can be incorporated in the future behavior analysis to envisage better performance.

Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU).

AIM: To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n >or= 228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes. METHODS: In total, 1041 adults (mean +/- sd), age 56 +/- 10 years, weight 82 +/- 17 kg and glycated haemoglobin (HbA(1c)) 8.4 +/- 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono : combination therapies (30 : 70%) to participate in a five-arm, 26-week, double-dummy, randomized study. RESULTS: Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA(1c) from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%). CONCLUSIONS: Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.

Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient.

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.

A low-GI diet is associated with a short-term improvement of glycaemic control in Asian patients with type 2 diabetes.

AIMS: The aim of this study is to compare the efficacy of low glycaemic index (GI) vs. conventional carbohydrate exchange (CCE) dietary advice on glycaemic control and metabolic parameters in patients with type 2 diabetes. METHODS: A total of 104 patients with type 2 diabetes were randomly assigned to either a low GI (GI) or CCE dietary advice over a 12-week period. The primary end-point was glycaemic control as assessed by glycated haemoglobin A1c (HbA1c), fructosamine level and plasma glucose. The secondary end-points were anthropometric measurements and metabolic parameters that include blood pressure, lipid profile and insulin levels. The oral antidiabetic medications remained unchanged throughout the duration of the study. RESULTS: A low-GI diet was associated with significant changes in the fructosamine level (DeltaGI = -0.20 +/- 0.03; DeltaCCE = -0.08 +/- 0.03 mmol/l, p < 0.01) and waist circumference (DeltaGI group = -1.88 +/- 0.30 cm; DeltaCCE group: -0.36 +/- 0.4 cm, p < 0.05) at week 4. At week 12, the changes in fasting glucose (DeltaGI = -0.03 +/- 0.3; DeltaCCE = 0.7 +/- 0.3 mmol/l; p < 0.05) and waist circumference (DeltaGI = -2.35 +/- 0.47 cm; DeltaCCE group = -0.66 +/- 0.46 cm; p < 0.05) in the GI group was significantly lower than the CCE group. With the low-GI diet, the changes in postprandial glycaemia at time 0, 60, 150 and 180 min after consuming the standard test meal was lower than with the CCE diet (p < 0.05). No significant differences were found between the groups for the remaining parameters that were measured. CONCLUSIONS: Use of a low-GI diet resulted in significant changes of serum fructosamine level, plasma glucose and waist circumference in Asian patients with type 2 diabetes over a 12-week period compared with those following a CCE diet. The effect on HbA1c and other metabolic parameters was not significantly different between the two study groups but the improvement within the GI group was more pronounced and of clinical benefit.

Steven Johnson syndrome in a patient with Cushing's disease.

Cushing's syndrome is a pathological condition associated with excessive cortisol production, the commonest etiology being Cushing's disease. Corticosteroids in high doses have been used in the management of Steven Johnson Syndrome (SJS) with favourable outcome. We describe a patient with Cushing's disease who developed SJS, one week after taking sperulina a product from sea-weed while waiting for transphenoidal surgery.

ACTH producing pulmonary carcinoid and pituitary macroadenoma: a fortuitous association?

We report a case of a 45 year-old man who presented initially with a non-functioning pituitary macroadenoma. A routine chest radiography done preoperatively revealed a right lung nodule which was confirmed by computed tomography (CT) of the thorax. Transfrontal hypophysectomy was performed while a conservative approach was taken for the lung nodule. Four years later, he presented acutely with adrenocorticotrophic hormone (ACTH) dependent Cushing's syndrome which resolved following a right lobectomy. Histological examination revealed an atypical carcinoid. To our knowledge, this is the first reported case of an ectopic ACTH secreting pulmonary carcinoid found in association with a non-functioning pituitary macroadenoma.

Methyl chanofruticosinates from leaves of Kopsia flavida Blume.

Three new indole alkaloids with methyl chanofruticosinates skeletal system, viz., methyl 12-methoxy-N1-decarbomethoxychanofruticosinate, methyl 12-methoxychanofruticosinate and methyl 11,12-dimethoxychanofruticosinate, in addition to methyl 11,12-methylenedioxy-N1-decarbomethoxychanofruticosinate, have been isolated from the leaves of Kopsia flavida Blume. The structures of these three new indole alkaloids were assigned by NMR spectral data using various 2D-techniques.

Regulation and tissue distribution of the human sodium iodide symporter gene.

OBJECTIVE: Iodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS). In the present report, we have analysed the factors that modulate human NIS mRNA expression and iodide uptake in primary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA tissue distribution was investigated. METHODS: Primary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72 h. Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and 125I uptake, respectively. Human tissue samples were investigated for NIS gene expression using both RT-PCR and Northern blotting. RESULTS: Human TSH increased both NIS gene expression and iodide uptake in TFC cultures in a dose-dependent manner. Using concentrations of 0.1 U/l of hTSH, a minor increase in NIS gene expression was detected without a detectable increase in iodide uptake. IL-1 alpha, TNF alpha and IFN gamma at concentrations of 10(5) U/l all inhibited TSH-induced NIS gene expression and iodide uptake. In these experiments, there was a good correlation between NIS mRNA expression and iodide uptake. Using RT-PCR higher levels of NIS mRNA were detected in Graves' disease (GD) compared to multi-nodular goitre tissue samples. Stomach and salivary gland tissue also expressed NIS mRNA, whereas low levels were found in the mammary gland and extraocular muscle tissue. No expression was detected in the ovary, oesophagus, colon, extraocular fat or skin. In contrast, Northern blot analysis failed to detect NIS in stomach, salivary gland, intestinal fat or non-toxic multi-nodular goitre tissue samples, although this was present in GD thyroid tissue. CONCLUSION: TSH upregulates sodium iodide symporter gene expression and iodide uptake in primary thyroid follicular cell cultures, and this induction is modulated by cytokines. Variable levels of sodium iodide symporter mRNA are present in different tissue samples, with high expression evident in Graves' disease thyroid tissue.