Association Between Copper Excess,Zinc Deficiency,and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley,India—A High Risk Area

Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India—a high incidence area. The average level of copper was significantly higher (P < 0.0001) for patients than for controls, with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. The control group consisted of 55 healthy individuals matched for age, sex, and place of residence of the patients. In contrast, the average level of zinc in patients was significantly lower than in controls (P < 0.0001), with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. The levels of both copper and zinc showed significant differences based on gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P < 0.0001). To validate the general notion that imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.     

Correction: prevalence and socioeconomic correlates of overweight and obesity among Pakistani primary school children

ABSTRACT: Since the publication of our article [1], we have noticed some errors in the final published version, for which the corresponding author accepts full responsibility. Page references are to the final PDF version. Page 3: Results, second paragraph Lines 1-2: "BMI... 20.7 (5.02) kg/m2..." should read "BMI... 16.0 (3.0) kg/m2..." Lines 6-8: "According to the IOTF cut-offs, overweight and obesity prevalence was 33% (95% CI 31.1-35.3) and 24% (95% CI 22.4-26.2) respectively" should read "According to the IOTF cut-offs, overweight and obesity prevalence was 8.3% (95% CI 7.1-9.6) and 4.7% (95% CI 3.8-5.7) respectively" Page 4: Table 1 The values for mean and standard deviation (SD) for BMI (kg/m2) are revised. Page 4: Table 2 The values for mean BMI (SD) and overweight and obesity prevalence according to the IOTF cut-offs are revised. Page 5: Figure 2 The values for grade- and gender- specific mean BMI are revised. Page 6: Second paragraph Lines 1-8: "Prevalence of overweight by the IOTF cut-offs was twice the prevalence by the WHO 2007 reference (33% versus 17%) and prevalence of obesity by the IOTF cutoffs was three times higher than that calculated by the WHO 2007 reference (24% versus 7.5%). Using IOTF cut-offs for overweight and obesity in Pakistani schoolaged children would result in higher estimates than the WHO 2007 reference." should read "Prevalence of overweight by the IOTF cut-offs was half the prevalence by the WHO 2007 reference (8% versus 17%) and prevalence of obesity by the IOTF cutoffs was two-third of that calculated by the WHO 2007 reference (5% versus 7.5%). Using IOTF cut-offs for overweight and obesity in Pakistani schoolaged children would result in lower estimates than the WHO 2007 reference. A relatively lower overweight and obesity prevalence with use of the IOTF cut-offs as compared to the WHO reference had been reported elsewhere [2-3]." In present study, the estimates for overweight included obese children.     

Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening

Arylamine N-acetyltransferases (NAT; EC 2.3.1.5) catalyse the transfer of acetyl groups from acetylCoA to xenobiotics, including drugs and carcinogens. The enzyme is found extensively in both eukaryotes and prokaryotes, yet the endogenous roles of NATs are still unclear. In order to study the properties of eukaryotic NATs, high-throughput substrate and inhibitor screens have been developed using pure soluble recombinant Syrian hamster NAT2 (shNAT2) protein. The assay can be used with a wide range of compounds and was used to determine substrate specificity of shNAT2. We describe the expression and characterisation of shNAT2 and also purified recombinant human NAT1 and NAT2, including the use of the assay to explore the substrate specificities of each of the enzymes. Hamster NAT2 has similar substrate specificity to human NAT1, acetylating para-aminobenzoate but not arylhydrazine and hydralazine compounds. The overlapping but distinct substrate-specific activity profiles of human NAT1 and NAT2 were clearly observed from the screen. Naturally occurring compounds were tested as substrates or inhibitors of shNAT2 and succinylCoA was found to be a potent inhibitor of shNAT2.     

Synthesis of Novel Pyrimidin‐4‐One Bearing Piperazine Ring‐Based Amides as Glycogen Synthase Kinase‐3β Inhibitors with Antidepressant Activity

Novel pyrimidin‐4‐one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase‐3β (GSK‐3β) inhibitors. Among all the synthesized compounds, compound 5 (3‐methyl‐6‐phenyl‐2‐(piperazin‐1‐yl)‐3,4‐dihydropyrimidin‐4‐one) exhibited the most potent inhibitory activity against GSK‐3β with IC₅₀ value of 74 nm . The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val‐135 to the active site of GSK‐3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK‐3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK‐3β with antidepressant activity.     

Molecular Study of Sheep Malignant Theileriosis at Barka Region in the Sultanate of Oman

Background

We used the PCR technique based on the abovementioned primer pair and sequencing to demonstrate the Theileria infection in the sheep samples collected from Sultanate of Oman.

Methods

According to the frame work of “integrated control of ticks and tick borne diseases in globalized world managed by EU-ICTTD-3 project, the samples from blood, liver, spleen, lymph node and lung were sent to the laboratory of Iranian Research Center for Ticks and Tick-borne Diseases (IRCTTD). Samples from blood smear and impression smears from liver, spleen, lymph node, and lung were analyzed by Geimsa staining. The DNA was extracted from the abovementioned samples and analyzed by PCR technique using specific primers derived from the nucleotide sequences of 18S rRNA gene of T. lestoquardi, which can amplify the common region in other Theileria and Babesia spp. Subsequently the amplified DNA was sequenced.

Results

The analysis of blood smears of the sheep was negative for piroplasmosis performed through the Giemsa staining. The impression smears prepared from liver, spleen, lymph node, and lung showed suspicious structures mimicking Theileria schizonts in some cells. The results showed an expected PCR product of 428 bp in length, which is specific for Theileria spp. The PCR products were subsequently sequenced. The corresponding nucleotide sequence is registered under accession number {"type":"entrez-nucleotide","attrs":{"text":"JF309152","term_id":"323695911","term_text":"JF309152"}}JF309152 in GenBank. The sequence alignment in GenBank showed that the PCR products had 99% homology to the known T. lestoquardi registered under accession number {"type":"entrez-nucleotide","attrs":{"text":"AF081135","term_id":"7576455","term_text":"AF081135"}}AF081135 in the GenBank.

Conclusion

Oman sheep are highly susceptible for Theileria infection and the infected sheep mostly die before the microschizonts or erythrocytic form of Theileria appears in the nucleated or erytrocytic cells respectively.     

Seroprevalence of Neospora spp. in Horses in North East of Iran

Background

Neospora caninum, an obligate intracellular protozoan parasite, is recognized as a major cause of abortion in cattle, while limited information is presently available on the seroprevalence of Neospora antibodies in horses’ worldwide. The aim of the present study was to determine serologic prevalence of Neospora infection in horses in Iran.

Methods

Sera from 150 horses from Mashhad suburb in Razavi Khorasan Province, northeast Iran were examined for antibodies to Neospora spp. using Neospora modified direct agglutination test (N-MAT).

Results

Antibodies to this parasite were detected in 45 (30%) of the examined serum samples. Thirty four percent of the samples had titer of 1:40 while then reduced to 30% when 1:80 serum dilution was applied as significant cut off titer.

Conclusion

This study is the first investigation carried out on the Neospora in horses in Iran and indicates that horses in Iran are exposed to this parasite.     

Ethnomedicinal knowledge of the most commonly used plants from Deosai Plateau,Western Himalayas,Gilgit Baltistan,Pakistan

Ethnopharmacological relevance

The current survey was aimed to identify the prime important medicinal plants in terms of medicines and further pharmacological screening of such plants. As far as, we know, no reported data from Deosai Plateau have been published and this is the first documented information of the study area.

Material and methods

Ethnomedicinal information of plants was collected through semi-structured interviews through a participatory rural appraisal (PRA) method.

Results and discussion

This study provided information of 50 medicinal plant species used to treat 29 different ailments. A total of 42 species (84%) were herbs while shrubs and subshrubs were represented by 8 species (16%). Leaves (37%) were the predominant plant parts followed by, roots (27%), aerial parts (13%), flowers (12%), fruit (7%), seeds (3%), and tuber (1%). Method of preparation fall into five categories including infusion (31%), paste (23%), decoction (20%), powder (18%), and juice (8%).

Conclusion

The study area is rich in medicinal plant diversity growing in wild. Our efforts in this regard are only a little contribution to the ethnobotanical study of this area focusing on medicinal plants while more clinical studies are required in future to prove such claims of local inhabitants.     

Necrotizing haemorrhagic pneumonia proves fatal in an immunocompetent child due to Panton–Valentine Leucocidin, toxic shock syndrome toxins 1 and 2 and enterotoxin C-producing Staphylococcus aureus

Panton–Valentine leucocidin (PVL) toxin-producing strains of Staphylococcus aureus ( S. aureus ) are associated with skin abscesses and furunculosis, with necrotizing pneumonia being a relatively rare problem. Here, we describe a fatal case of necrotizing pneumonia in a 14-year-old child who presented initially with sore throat and pyrexia. He deteriorated rapidly, developing hypotension, multiple organ failure and purpura fulminans. S. aureus was isolated from the tracheal aspirate, which was found to be positive for PVL, toxic shock syndrome toxins (TSST) 1 and 2 and staphylococcal enterotoxin C (SEC). It was postulated that purpura fulminans and toxic shock syndrome were a result of the abovementioned exotoxins.
Conclusion: This case highlights the emergence of PVL-positive community-acquired S. aureus infection and association of purpura fulminans with superantigens. Practitioners should be aware of this illness in order to initiate appropriate treatment.     

An update on the management of Wilms' tumour.

AIMS: To review the management of Wilms' tumour. METHODS: A search of the literature was performed using the PubMed database (1966 to May 2006) with the search terms 'Wilms' and either 'tumour/tumor' or 'cancer' or 'carcinoma'. This was augmented by manual searches of publications. FINDINGS: The success of clinical trials in Wilms' tumour patients over the past 30 years has led to an overall survival of 85% and the introduction of less aggressive chemotherapeutic regimes for patients. Large randomised controlled trials have been published on the management of Wilms' tumour by various collaborative groups, including the National Wilms' Tumour Study Group (NWTSG) in North America and the Société Internationale d'Oncologie Pédiatrique (SIOP) plus the United Kingdom Children's Cancer Study Group (UKCCSG) in Europe. CONCLUSIONS: Controversy exists as to the best approach to the management of these children with regard to neoadjuvant chemotherapy. Challenges remain in the identification of histological and molecular risk factors for the stratification of treatment intensity.