Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

Seropositivity of Human Brucellosis among Patients with Pyrexia of Unknown Origin on Both Risk and Non-Risk Group of Individuals and Molecular Detection by Real-time PCR.

Brucellosis is a zoonotic disease that is one of the important infectious causes of Pyrexia of Unknown Origin (PUO). The objective of the present study was to determine the seropositivity and molecular detection of human brucellosis among the patients with pyrexia of unknown origin on both risk and non-risk group of individuals in greater Mymensingh. A total of 400 blood samples were randomly collected from pyretic patients started from September 2018 to August 2019. Questionnaires were used to collect data on both risk and non-risk group of individuals. All samples were initially screened for anti-Brucella antibodies using the Brucella-specific latex agglutination test. For accurate investigation, seropositive as well as seronegative serum samples were tested by BCSP31 Brucella genus-specific TaqMan real-time PCR. Overall 32(8%) cases were positive out of 400 samples by Brucella-specific latex agglutination test and/or BCSP31 Brucella genus-specific real-time PCR. Brucella-specific latex agglutination test documented 7% (28/400) positivity for brucellosis. 22(5.5%) samples found Brucella genus-specific real-time PCR positive out of 400 samples. Most real-time PCR positive cases were found from sero-positive samples of risk group population (15/32). Sero-negative but real-time PCR positive cases also found only from risk group population (4/32). There were 10 seropositive cases where real-time PCR was negative. In addition to Brucella-specific latex agglutination test as a screening test, Brucella genus-specific real-time PCR was performed for confirmation and also to avoid unjustified costs, drug toxicity, and masking of other potentially dangerous diseases.

Assessment of vaccination with gamma radiationattenuated infective Toxocara canis eggs on murine toxocariasis.

Toxocara canis is a major parasite that infects many animals with high risk of human infections. This study aims at assessing the immunization with gamma radiationattenuated infective stage on rats challenged with non-irradiated dose. Level of vaccine protection was evaluated in liver and lung regarding parasitological, histopathological, biochemical and molecular parameters. Fifty rats were enrolled in three groups: group A (10 rats) as normal control; group B (20 rats) subdivided into subgroup B1 (infected control) and subgroup B2 infected then challenged after 14 days with the same dose of infection (challenged infected control); and group C (20 rats) subdivided into subgroup C1 vaccinated with a dose of 800 gray (Gy) gamma-radiated infective eggs (vaccine control) and subgroup C2 vaccinated then challenged on 14th day with same number of infective eggs (vaccinated-challenged). Tissues were stained with Haematoxylin and Eosin (H and E) for histopathological studies. Biochemical studies through detection of nitric oxide (NO) and Caspase-3 were conducted. Extent of DNA damage by Comet assay was assessed. Vaccinated-challenged subgroup revealed a marked reduction in larvae in tissues with mild associated histological changes. In addition there was accompanied reduction of NO, Casepase-3 level and DNA damage compared to the control infected group. It could be concluded that vaccination of rats with a dose of 800Gy gamma radiation-attenuated infective stage improves immune response to challenge infection and drastically reduces the morbidity currently seen.

Assessment of vaccination with gamma radiation-attenuated infective Toxocara canis eggs on murine toxocariasis

@#Toxocara canis is a major parasite that infects many animals with high risk of human infections. This study aims at assessing the immunization with gamma radiationattenuated infective stage on rats challenged with non-irradiated dose. Level of vaccine protection was evaluated in liver and lung regarding parasitological, histopathological, biochemical and molecular parameters. Fifty rats were enrolled in three groups: group A (10 rats) as normal control; group B (20 rats) subdivided into subgroup B1 (infected control) and subgroup B2 infected then challenged after 14 days with the same dose of infection (challenged infected control); and group C (20 rats) subdivided into subgroup C1 vaccinated with a dose of 800 gray (Gy) gamma-radiated infective eggs (vaccine control) and subgroup C2 vaccinated then challenged on 14th day with same number of infective eggs (vaccinated-challenged). Tissues were stained with Haematoxylin and Eosin (H&E) for histopathological studies. Biochemical studies through detection of nitric oxide (NO) and Caspase-3 were conducted. Extent of DNA damage by Comet assay was assessed. Vaccinated-challenged subgroup revealed a marked reduction in larvae in tissues with mild associated histological changes. In addition there was accompanied reduction of NO, Casepase-3 level and DNA damage compared to the control infected group. It could be concluded that vaccination of rats with a dose of 800Gy gamma radiation-attenuated infective stage improves immune response to challenge infection and drastically reduces the morbidity currently seen.

Molecular characterization of Orientia tsutsugamushi causing scrub typhus among febrile patients in north-central Bangladesh.

Scrub typhus is a mite-borne rickettsial disease caused by Orientia tsutsugamushi, which is endemic in Asia Pacific region. In this study, infection rate and molecular epidemiologic traits of O. tsutsugamushi was investigated in Mymensingh, located in north-central Bangladesh. Among the blood samples from 453 febrile patients who visited Mymensingh medical college hospital in 2018, the 47 kDa protein gene of O. tsutsugamushi was detected in 78 samples (17.2%) by nested PCR. Phylogenetic analysis of the O. tsutsugamushi 56 kDa protein gene (18 samples) revealed a predominance of Karp-related genotype (89%), while the remaining belonged to Gilliam genotype. Samples of the Karp-related genotype mostly clustered with those of China, Taiwan, Thailand and India, etc., in emergent subgroups clades 2 and 4, which were distinct from clade 1, including prototype Karp strains. Among the 18 samples, three variable domains (VD) of 56 kDa type-specific antigen had different types of sequence diversity; VDI contained two or three repeats of eight amino acid units, while VDII and VDIII had amino acid substitution, deletion or insertion. The present study documented a potentially high prevalence of genetically diverse O. tsutsugamushi in north-central Bangladesh.

Effect of vaccination with irradiated Toxocara canis larvae or thyme oil treatment on testicular histochemical and immunohistochemical changes of rats.

Toxocara canis is widely distributed parasite that not only presents in definitive hosts but also occurs in paratenic hosts including human. Larvae migrate throughout the somatic tissue causing severe inflammatory and pathological reactions. This study aims to detect the effect of infection with Toxocara canis on testis of rats regarding histopathological, histochemical and immunohistochemical changes and amelioration of these changes with either vaccination with gamma radiation-attenuated embryonated eggs or with herbal treatment with thyme. The study was conducted on eighty rats classified into four groups (20 each): Group A (normal control); Group B (infected control); Group C infected and treated with thyme oil (thyme-treated); and Group D vaccinated with 800 Gy gamma radiation-attenuated embryonated eggs, and challenged with the same number of eggs (vaccinated-challenged). Testicular tissues were stained with Haematoxylin and Eosin (H and E) for histopathological study. Periodic acid Schiff's (PAS), bromophenol blue (BPB) and Feulgen's reaction for carbohydrates, proteins and DNA, respectively were done to examine histochemical changes. Immunohistochemical study was done through expression of TGF-ß1 and caspase-3. Infected control group B showed severe histopathological changes with marked decrease in PAS +ve materials, total proteins and DNA and enhanced expression of Transforming growth factor- ß1 (TGF-ß1) and caspase-3. Moderate changes were observed in testicular tissues of group C treated with thyme. Slight changes were detected in vaccinated-challenged group D. It was concluded that Toxocara canis infection causes marked hispathological, histochemical and immunohistochemical changes in testicular tissues of rats that can be ameliorated by vaccination with radiation-attenuated infective stage or treated with thyme; however vaccination is more effective in protection.

Effect of vaccination with irradiated Toxocara canis larvae or thyme oil treatment on testicular histochemical and immunohistochemical changes of rats

@#Toxocara canis is widely distributed parasite that not only presents in definitive hosts but also occurs in paratenic hosts including human. Larvae migrate throughout the somatic tissue causing severe inflammatory and pathological reactions. This study aims to detect the effect of infection with Toxocara canis on testis of rats regarding histopathological, histochemical and immunohistochemical changes and amelioration of these changes with either vaccination with gamma radiation-attenuated embryonated eggs or with herbal treatment with thyme. The study was conducted on eighty rats classified into four groups (20 each): Group A (normal control); Group B (infected control); Group C infected and treated with thyme oil (thyme-treated); and Group D vaccinated with 800 Gy gamma radiation-attenuated embryonated eggs, and challenged with the same number of eggs (vaccinated-challenged). Testicular tissues were stained with Haematoxylin and Eosin (H &E) for histopathological study. Periodic acid Schiff’s (PAS), bromophenol blue (BPB) and Feulgen’s reaction for carbohydrates, proteins and DNA, respectively were done to examine histochemical changes. Immunohistochemical study was done through expression of TGF-β1 and caspase-3. Infected control group B showed severe histopathological changes with marked decrease in PAS +ve materials, total proteins and DNA and enhanced expression of Transforming growth factor- β1 (TGF-β1) and caspase-3. Moderate changes were observed in testicular tissues of group C treated with thyme. Slight changes were detected in vaccinated-challenged group D. It was concluded that Toxocara canis infection causes marked hispathological, histochemical and immunohistochemical changes in testicular tissues of rats that can be ameliorated by vaccination with radiation-attenuated infective stage or treated with thyme; however vaccination is more effective in protection.

Fecal microbiota profile in atopic asthmatic adult patients.

Summary: Background. Studies proposed a link between gut microbiota and airway tract. Objective. Study the diversity and density of gut microbiota in healthy and asthmatic patients. Method. Semi-quantitative stool cultures were performed from fecal samples collected from 80 adult asthmatic patients and 40 healthy individuals. Data on gender, age, dietetic history, clinical examination and investigations as skin prick test and pulmonary function testing were also collected. Results.Lactobacilli were found to be higher among patient group than control group. E. coli density was statistically higher in patient than control group. No significant difference was detected between male and female patients or controls. Lactobacilli were statistically more prevalent in stool culture of male cases than that of male controls. No difference was found between female cases and controls. There was no relationship between type of microbial growth and disease related parameters including age, duration of illness, number of allergens and pulmonary function test in cases. Conclusion. Atopic asthma is significantly associated with gut microbiota Lactobacilli and E. coli. It is important to determine the organism involved, to focus on microbiome-driven disease and therapies.

Content specificity of attentional bias to threat in post-traumatic stress disorder.

BACKGROUND: Attentional bias to affective information and reduced cognitive control may maintain the symptoms of post-traumatic stress disorder (PTSD) and impair cognitive functioning. However, the role of content specificity of affective stimuli (e.g., trauma-related, emotional trauma-unrelated) in the observed attentional bias and cognitive control is less clear, as this has not been tested simultaneously before. Therefore, we examined the content specificity of attentional bias to threat in PTSD. METHODS: PTSD participants (survivors of a multistory factory collapse, n=30) and matched controls (n=30) performed an Eriksen Flanker task. They identified the direction of a centrally presented target arrow, which was flanked by several task-irrelevant distractor arrows pointed to the same (congruent) or opposite direction (incongruent). Additionally, participants were presented with a picture of a face (neutral, emotional) or building (neutral=normal, emotional=collapsed multistory factory) as a task-irrelevant background image. RESULTS: We found that PTSD participants produced overall larger conflict effects and longer reaction times (RT) to emotional than to neutral stimuli relative to their healthy counterparts. Moreover, PTSD, but not healthy participants showed a stimulus specific dissociation in processing emotional stimuli. Emotional faces elicited longer RTs compared to neutral faces, while emotional buildings elicited faster responses, compared to neutral buildings. CONCLUSIONS: PTSD patients show a content-sensitive attentional bias to emotional information and impaired cognitive control.

Novel effect of Daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats.

This study was designed to evaluate the hepato and neuroprotective activity of Daflon and low-dose γ radiation on thioacetamide (TAA)-induced liver damage and hepatic encephalopathy (HE) in rats. Effect of daily Daflon treatment (100 mg/kg body weight, Per OS (p.o.) for consecutive 3 days) and/or fractionated low-dose γ-radiation (LDR; 0.25 Gy, twice the total dose of 0.5 Gy at the 1st and 3rd day, respectively) was evaluated against TAA (300 mg/kg, intraperitoneal × 3) induced liver damage and HE in rats. Serum aspartate transaminase, alanine transaminase, γ-glutamyltransferase, total bilirubin, ammonia, and manganese were estimated to evaluate liver function. In addition, malondialdehyde (MDA) as well as reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were determined to assess antioxidant capacity in liver tissue. Moreover, hepatic apoptotic markers (cysteine-dependent aspartate-directed proteases 3, 8 (caspase-3, 8) and cytochrome C) were estimated to indicate hepatic apoptosis. HE was evaluated through the determination of whole brain ammonia, manganese, MDA, GSH, GPX, SOD, CAT, and caspase-3. The cognitive and locomotor deficits were assessed via step through passive avoidance test, activity cage (actophotometer), γ-aminobutyric acid, and N-methyl-d-aspartate/adenosine triphosphate-neuronal nitric oxide synthase/nitric oxide-cyclic guanosine monophosphate axis in rats' cerebella and hippocampi. The involvement of hypoxia inducible factor-1α, aquaporine-4, and matrix metalloproteinase 9 in association with the brain water content (%) in the whole brain as an index for brain edema was also evaluated. The obtained results showed a marked amelioration of the aforementioned biochemical parameters and behavioral tasks which is supported by histopathological and immunohistochemical examination. It could be concluded that Daflon and LDR afforded hepatoprotection and neuroprotection against TAA-induced acute liver damage and HE.

Prenatal maternal lipopolysaccharide administration leads to age- and region-specific oxidative stress in the early developmental stage in offspring.

Prenatal exposure to lipopolysaccharide (LPS) has been exploited to simulate brain disorder in animal model. Prenatal LPS-exposure has shown elevated levels of pro-inflammatory cytokines in the early stages of the postnatal period. This study determines the effect of prenatal LPS-exposure on oxidative stress (OS) in the distinct brain regions in the early postnatal stages. LPS (50 µg/kg, i.p.) and water for injection (100 µl, i.p.) were given to the experimental (n=5) and control (n=5) group of pregnant Swiss albino mice respectively on gestational day (GD)-16 and 17. Animals were decapitated on postnatal day (PnD) - 1, 7, 14 and 21 to assay levels of oxidative markers from 6 distinct brain regions. When compared with the control, prenatal LPS-exposure alters levels of OS markers: (i) on PnD-1, glutathione (GSH) level is raised and superoxide dismutase (SOD) activity is dropped, (ii) on PnD-7, advanced oxidation of protein product (AOPP) level is elevated, (iii) on PnD-14, lipid peroxidation (MDA) and activity of catalase (CAT) are enhanced, (iv) on PnD-21, increased MDA continued. The hippocampus (HC) and cerebellum (CB) were mostly susceptible to OS in the early postnatal development. Levels of MDA and activity of CAT enzyme were increased on PnD-14 in the cortex, HC and CB. Except MDA, all OS markers recovered and returned to the level of control animals on PnD-21. Taken together, these results suggest that prenatal LPS-exposure induces age- and region-specific OS in the early postnatal stage.

Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum.

We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid-induced writhing and formalin). The analgesic activity was compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous literature review it can be concluded that flavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent.

Tratamento endodôntico convencional de dente invaginado com periodontite apical / Conventional endodontic treatment of a dens invaginatus with apical periodontitis

Dente invaginado é uma anomalia do desenvolvimento caracterizada por invaginação dos tecidos dentários que varia de ligeiro aumento da fosseta do cíngulo a um profundo sulco que pode se estender até o ápice dentário. O objetivo deste trabalho foi discutir um caso clínico de dente invaginado tipo II em incisivo lateral superior em que foi realizado o tratamento endodôntico convencional. Posterior ao acompanhamento de 11 anos e frente aos exames clínicos e imaginológicos observou-se tratamento endodôntico satisfatório e regressão da rarefação óssea. Baseado nisso, foi possível concluir que o tratamento endodôntico convencional é uma alternativa viável para tratamento de dente invaginado tipo II.

Dens invaginatus is a developmental anomaly characterized by invagination of the dental tissues ranging from slight rise of the pit to a depth of the cingulate sulcus and can be extended to the apical portion of the tooth. The aim of this study was to relate a case of dens invaginatus type II in upper lateral incisor in which a conventional treatment was realized. After eleven years-follow up and based on clinical and images exams, it was observed that the endodontic treatment was efficient and the bone rarefaction reduced. Based on this, it was possible to conclude that conventional endodontic treatment is a viable alternative for type II dens invaginatus.

Immediate release three-layered chewing gum tablets of fenoprofen calcium: preparation, optimization and bioavailability studies in healthy human volunteers.

A three-layered gum tablet (1800 mg), containing 200 mg of Fenoprofen Calcium (Fn) with an inner core containing the drug, and two external layers containing antiadherent lubricant, has been prepared using direct compression. A 2(3) factorial plan has been designed to evaluate the effect of formulation variables namely, Pharmagum(®) M concentration, Maltodextrin type, and Co-adjuvant type on the release characteristics of Fn from the prepared tablets. The formula consisting of 65% Pharmagum(®) M, 75% Maltodextrin DE 39 and 5% Talc comparatively exhibited the highest release (66.59% ± 2.39) in the mouth after 5 min of chewing. Binary and ternary ß-cyclodextrin (ß-CD) complexation was adopted to enhance the release of Fn from the selected gum tablet. The highest significant release (p < 0.05) was achieved from the lyophilized ternary complex containing 100 mg of Fn in presence of polyvinylpyrrolidone (PVP K(25)), exhibiting a release of 88.25% ± 0.93 after 5 min of chewing. The relative bioavailability of the selected gum tablet was found to be 166.06% compared to Nalfon(®) 200 mg capsules. Reduction of the dose to 100 mg exhibited faster absorption rate than Nalfon(®) capsules. The obtained results suggest the possibility of reducing the dose of Fn in chewing gum.

Comparative study on the different techniques for the preparation of sustained-release hydrophobic matrices of a highly water-soluble drug.

The objective of the present study was to control the release of freely water-soluble salbutamol sulphate (SS) over a prolonged period of time by embedding the drug into slowly eroding waxy matrix materials such as Precirol® ATO5, Compritol® 888 ATO, beeswax, paraffin wax, carnauba wax, and stearyl alcohol. The matrices were prepared by either direct compression or hot fusion techniques. The compatibility of the drug with the various excipients was examined using differential scanning calorimetry (DSC). A factorial design was employed to study the effect of polymer type, polymer concentration (15% and 35%), and filler type (Avicel® PH101 and dibasic calcium phosphate dehydrate (DCP) on the in vitro drug release at 6 h. Results of DSC confirmed drugexcipient compatibility. Increasing the polymer ratio resulted in a significant retardation of drug release. The use of DCP resulted in significant retardation and incomplete drug release while the use of Avicel did not. The hot fusion method was found to be more effective than the direct compression method in retarding SS release. A Precirol formulation, prepared using the hot fusion technique, had the slowest drug release, releasing about 31.3% of SS over 6 h. In contrast, Compritol, prepared using the direct compression technique, had the greatest retardation, providing sustained release of 59.3% within 6 h. A hydrophobic matrix system is thus a useful technique for prolonging the release of freely water-soluble drugs such as salbutamol sulphate.

Sero-surveillance for orf antibodies in sheep and goats in Saudi Arabia employing the ELISA technique.

A serological survey was conducted on sheep and goats in Saudi Arabia to detect humoral antibodies against the orf virus. The ELISA technique was superior to the AGID and CFT in detecting such antibodies. Of the 239 abattoir serum samples examined, 60 per cent had orf antibodies by ELISA while 94.8 per cent of the convalescent sera had antibodies detectable by ELISA. With the lack of vaccination and the reports that the clinical disease is commonly seen in different parts of the Kingdom, it may be that orf is becoming enzootic in this country. Recommendations for implementing a satisfactory vaccination regimen are given.

Protection conferred by vaccination with Blacksburg and Komarov strains of Newcastle disease virus against Newcastle disease in Bangladesh.

An evaluation was undertaken of the efficacy of vaccination of day-old chicks with the Blacksburg (B1) strain of Newcastle disease virus (NDV) followed at various times by vaccination with the Komarov (K) strain. Antibody was detected by the haemagglutination inhibition (HAI) test one week after vaccination with B1 and titres peaked at three weeks and had declined to undetectable levels by nine weeks. After subsequent vaccination with K strain at five, seven or eight weeks of age levels of HAI antibody (titre 80 to 640) were detected after three weeks. Birds vaccinated at seven weeks were tested for antibody and resistance to challenge beyond 19 weeks of age. In this group the HAI titres remained constant (80 to 640) up to 32 weeks of age and then steadily declined to 10 to 20 at 44 weeks of age. A linear relationship between HAI titre and virus neutralising index (VNI) was demonstrated with a range of selected sera. Only birds with an HAI titre of 80 or greater resisted artificial challenge. It is recommended that, following B1 vaccination at day-old and K vaccination at seven weeks old, revaccination with K strain should be performed at intervals of not more than seven months.

Changes in distribution of some crucial elements in masseter myofibers following surgically induced trauma.

Experimentally induced surgical trauma of the masseter muscle in rats led to changes in the distribution of some crucial intracellular elements as determined by microprobe analysis. Sulfur, phosphorus, and potassium values were lowered while sodium and chlorine levels were elevated. These changes were accompanied by increased formation of ice crystal artifacts in myofibers. The findings suggest that trauma causes alterations in cytoplasmic macromolecules and in the state of water in the cells. The method of analysis provides a means for the further evaluation of antiinflammatory drugs.