Journal of Pathobiology Reaearch
Volume:24 Issue: 2, Summer 2021

Thyrotoxicosis is the name given to the clinical manifestations of the excess of thyroid hormones in the bloodstream. Thyrotoxicosis may induce increased fasting blood sugar (FBS) in patients of all ages, and has been reported in only few cases. The previous studies have shown that the prevalence of glucose intolerance in hyperthyroidism is 44-65% and may reverse to normal values after achieving euthyroid status. We discuss a 34-year-old woman who presented with thyrotoxicosis with enhanced FBS. The patient had a mild elevated FBS (110 mg/dl) when she had a severe thyrotoxicosis. After treatment with methimazole blood glucose level decreased to 85 mg/dl and by the third visit glucose level decreased to 82 mg/dl. It could be concluded that Mild hyperglycemia may co-exist with thyrotoxicosis and reduce to normal when the patient becomes euthyroid. Thus, early detection and treatment of thyroid hormones oversecretion can resolve the complications of both thyrotoxicosis and associated hyperglycemia.

Trying to treat COVID-19 patients has caused serious problems for the scientists. There are many routinely used drugs in clinical settings without definite effects, and more studies should be done so as to reach a successful treatment for COVID-19. Our aim is to evaluate four suggested chemicals using virtual analysis tools based on the drug-screening approach and application of cheminformatics, pharmacotoxicology and docking. Four repurposed drugs: rizatriptan, dasabuvir, pravastatin, and empagliflozin are used in the study. The 3D structure of COVID-19 Main Protease (M Pro) was obtained from protein data bank (PDB) with PDB code: 6LU7, as the target of binding site screening. Besides, cheminformatics, pharmacotoxicology and human proteins targets for each drug was evaluated using SwissADME interface, SwissTarget Prediction web server, toxicity estimation software tool (T.E.S.T) and Toxtree-v3.1.0.1851 offline software. The docking scores (DOS) were -139.399, -125.707, -102.183 and -99.6642 for dasabuvir, rizatriptan, empagliflozin and pravastatin, respectively. In addition, the quantitative structure-activity relationship (QSAR) and pharmacotoxicologic evaluations show dasabuvir has more acceptable results than the others. Human protein target-exploration show that rizatriptan interacts with G protein-coupled receptor and kinase enzymes, pravastatin targets the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, while empagliflozin interacts with sodium/glucose cotransporters (SLC). But, dasabuvir targets human protein with too low scores. Virtual screening applied to four potential anti-COVID-19 drugs shows that dasabuvir may be a safer and efficient agent, regarding pharmacotoxicology and therapeutic purposes. However, virtually screened agent/s should be evaluated by experimental models for ultimate confirmation.

A case-control study was designed to investigate the association between the risk of colorectal cancer and genetic variation in four single-nucleotide polymorphism (SNPs) within genes involved in folate metabolism: C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR), A66G of methionine synthase reductase (MTRR), and A2756G of methionine synthase (MTR). Genomic DNA was extracted from peripheral blood of 80 patients with newly diagnosed colorectal cancer and 100 non-cancer controls. The statistical analysis was done by logistic regression. The results showed that the MTR and MTRR SNPs were significantly associated with an increased risk of colorectal cancer (p<0.01). Moreover, no significant association was found between MTHFR C677T and MTHFR A1298C polymorphisms and the risk of colorectal cancer. These findings suggest that the MTRR A66G and MTR A2756G polymorphisms might be some genetic risks factor for colorectal cancer in the studied population.

Mucopolysaccharidosis (MSII) is described as a metabolic disorder resulting from an enzymatic failure causing from mutations in IDS gene, MPSII is divided into two forms; mild and severe. The first form does not affect intelligence and patients show no neurologic involvements, usually survive for the fourth decade of life. In patients with severe form, death mostly occurs due to neurologic involvement during the second decade of life. We reported a case, a 31-year-old patient, clinically suspicious to MPS II which was primarily diagnosed by the presence of the increased levels of dermatan and heparan sulfate in urine and I2S deficiency in plasma. Whole exome sequencing was utilized to detect the disease-causing variant in our patient. A de novo mutation (c.253G>A, (p.A85T) in exon 3 of the IDS gene was identified, which probably can describe the mild form of MPSII and clinical manifestations observed in the patient.

Maternal separation (MS) is a model to induce early life stress (CNS) and is related to increased levels of anxiety and cognitive deficiencies. Voluntary exercise has been shown to be associated with learning and memory improvement in behavioral tests and electrophysiological experiments. Since it plays a significant role in learning and memory and enhances synaptic plasticity, the authors hypothesized that voluntary exercise may affect MS-induced changes in synaptic plasticity and cognitive performance. Rat pups underwent the MS protocol for 180 min/day from postnatal day (PND) 1 to 21. Voluntary exercise was performed in the exercise (Ex and MS + Ex groups from PND 29 to 49. Anxiety-like behavior, learning and memory were measured in adolescent rats. In addition, evoked field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region of the hippocampus.MS induced higher anxiety-like behavior as well as impaired learning and memory, but did not affect locomotor activity. Voluntary exercise improved MS-induced deficits and increased the learning and memory of MS rats. It also decreased anxiety-like behavior in the open field test. The results revealed that long-term potentiation (LTP) was induced in all groups, except for MS. However, voluntary exercise induced LTP and had maintenance in MS + Ex.

Regarding to chronic nature of epilepsy, side effects and resistance to chemical drugs, and with the objective to access to more effective treatment procedures, herbal medicine have received remarkable interest. The aim of this study was to determine the anticonvulsant effects of hydro-alcoholic extract of Cichorium intybus leaves on PTZ-induced seizure in male mice.

In this experimental study, 56 albino male mice weighing 20-25 g were divided randomly into seven groups. All groups were injected intraperitoneally. The negative and positive control groups received saline (10 ml/1000g) and Phenobarbital (40mg/kg) respectively. Treatment groups received hydro – alcoholic extract of Cichorium intybus leaves at doses of 100, 300, 500, 800 and 1000 mg/kg. All injections were carried out 45 minutes prior to the experiment. In order to provoke convulsion, after 45 minutes pentylenetetrazol (PTZ) was injected (80 mg/kg) to all groups and initiation time of myoclonic and tonic-clonic seizures and percent of 24 h death were measured.

The results indicated that the extract delayed the initiation time of myoclonic and tonic-clonic seizures in comparison with control group. The delay was significant at doses of 1000 and 800 mg/kg (P < 0.001) and 500 mg/kg (P < 0.01) for myoclonic seizure and 1000, 800 and 500 mg/kg (P < 0.001) and 300 mg/kg (P < 0.05) for tonic-clonic seizure. Also, the extract decreased the 24 h death.

It seems the hydro-alcoholic extract of Cichorium intybus have decremental effect on PTZ-induced seizure.

currently TB diagnosis is limited by some major limitations in low-income and less experienced hospitals. Recently, it has been proposed that the ku gene of mycobacterial strains has the potential to be a highly specific and sensitive candidate biomarker for molecular detection of Mycobacterium tuberculosis (Mtb). This study was aimed to evaluate the specificity and sensitivity of a real-time PCR assay for detection of ku gene in Mtb complex to determine its applicability for Mtb identification.

The identification of Mtb was confirmed using GeneXpert assay. Specific primers for ku gene were designed and the cycle threshold (Ct) value from the real-time PCR was used as a proxy measure of the cut-off point. Receiver operating characteristic (ROC) curve analysis was conducted to determine the diagnostic performance of ku gene in detecting Mtb directly from clinical specimens.

ku amplification was interpreted as positive and negative based on Ct values, in which a value <38 was considered positive and a value >40 was considered negative. Our findings revealed that the ku gene was found to be distributed in all Mtb-positive samples. Of note, none of the Mtb-negative exhibited a specific signal in a maximum of 40 cycles.

The ku gene amplification using real-time PCR indicated high sensitivity and specificity for the detection of Mtb complex in sputum samples.

Vibrio cholerae, the causative agent of cholera, has attracted a great deal of attention as one of the major causes of morbidity and mortality worldwide, especially in developing countries. In most laboratories, biochemical assays are primarily performed for possible detection of these strains, which are then followed by a PCR (polymerase chain reaction) test to verify their identity. This study aimed to optimize dot blot technique to detect Vibrio cholerae bacteria for V. cholera as an easy-to-use and beneficial method.

 A dot blot hybridization test was developed in this study to identify V. cholerae isolates as well as to assess the sensitivity and specificity of this test compared whit biochemical and PCR tests routinely performed for V. cholerae screening and detection in clinical specimens.

Herein, the dot blot hybridization test was optimized to detect V. cholerae. A combination of three biochemical assays and PCR test confirmed the results of dot blot hybridization test. This test was able to identify V. cholerae strains with a high sensitivity and specificity of 100%. Using the newly developed method, a set of 26 V. cholerae isolates collected from clinical samples were accurately identified.

This study optimized dot blot technique as a simple and useful assay that could be employed in V. cholerae monitoring programs and strategies to effectively detect V. cholerae strains in surface water and fecal specimens.