Relationship between tooth type and material used in the construction of endocrowns and fracture force values: a systematic review.

OBJECTIVE: The aim of this study was to summarize the results of the endocrown (EC) studies that compared tooth preparation designs, tooth types, and ceramic material types in relation to fracture force values. MATERIALS AND METHODS: A full literature search was conducted in Web of Science, PubMed/Medline, EMBASE, Scopus, Cochrane Library, Google Scholar, and ProQuest electronic databases. The following keywords: Endocrown [(molar(s)) or (premolar(s) or (posterior teeth)] and Ceramic materials as (Lithium disilicate glass-ceramic; Zirconia; Lava Ultimate) and (fracture strength) or (fatigue) were used. Articles were manually searched utilizing their reference lists. Study selection was not restricted or limited to the time of publication, type of tested tooth, ceramic material, and EC design. RESULTS: A total of 34 laboratory studies published between 2008 and 2023 were included in this systemic review. Twelve studies were published in the last 3 years, the mandibular molar was examined by 14 studies, and premolars in both arches were investigated, followed by premolars in both arches. Lithium disilicate glass-ceramic (LDGC) was the most used material for EC testing, followed by LAVA Ultimate and zirconia materials. The EC design with a 2 mm extension inside the pulp (14 studies) was the most used. Fracture forces of maxillary molars or premolars were nearly equal and lower than those of mandibular molars. Differences among the fracture forces of the tested ceramic materials were marginal. EC with 2 mm deep inside the pulp showed the highest fracture force. CONCLUSIONS: Mandibular EC molars showed the highest fracture forces, followed by maxillary premolars and molars. No differences among the EC materials in the 2- and 4-mm pulpal extension designs were found, which had higher fracture forces than other designs.

Synthesis, in-Silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent.

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski's rule of five. The compounds 6e and 6m showing the best results in OGTT were evaluated for in-vivo anti-diabetic evaluation in STZ induced diabetic rats. Administration of 6e and 6m for four weeks decreased the blood glucose levels significantly. Compound 6e (4.5 mg/kg p.o.) was the most potent compound of the series. It reduced the level of blood glucose to 145.2 ± 1.35 compared to the standard Pioglitazone (150.2 ± 1.06). Moreover, the 6e and 6m treated group did not show increase in bodyweight. The biochemical estimations showed that the levels of ALT, ASP, ALP, urea, creatinine, blood urea nitrogen, total protein and LDH restored to normal in 6e and 6m treated groups as compared to STZ control group. The histopathological studies supported the results obtained in biochemical estimations. Both the compounds did not show any toxicity. Moreover, the histopathological studies of pancreas, liver, heart and kidney revealed that the structural integrity of these tissues restored to almost normal in 6e and 6m treated groups as compared to STZ control group. Based upon these findings it can be concluded that the pyrimidine-based thiazolidinedione derivatives represent novel anti-diabetic agents with least side effects.

Spectral analysis and Antibacterial activity of the bioactive principles of Sargassum tenerrimum J. Agardh collected from the Red sea, Jazan, Kingdom of Saudi Arabia / Análise espectral e atividade antibacteriana dos princípios bioativos de Sargassum tenerrimum J. Agardh coletados no mar Vermelho, Jazan, Reino da Arábia Saudita

Seaweeds are a major marine resource that can be explored to develop novel pharmaceutical molecules. The present study showed the presence of unique bioactive components in the petroleum ether extract (PEE) and methanolic extract (ME) of Sargassum tenerrimum. The gas chromatography-mass spectrometry analysis suggested that the PEE of S. tenerrimum contained antibacterial biomolecules: hexadecanoic acid, methyl ester, 17-pentatriacontene, dasycarpidan-1-methanol, and acetate (ester). However, the ME of S. tenerrimum exhibited better antibacterial effect than the PEE due to the presence of the bioactive compounds 1,2-benzenedicarboxylic acid, diisooctyl ester, tetratetracontane, 1-docosene, 1,2-benzenediol, and benzoic acid. Thus, promising antibacterial molecules can be isolated from S. tenerrimum for better therapeutic use.

As algas marinhas são um importante recurso marinho que pode ser explorado para desenvolver novas moléculas farmacêuticas. O presente estudo mostrou a presença de componentes bioativos únicos no extrato etéreo de petróleo (PEE) e no extrato metanólico (ME) de Sargassum tenerrimum. A análise por cromatografia gasosa espectrometria de massa sugeriu que o PEE de S. tenerrimum continha biomoléculas antibacterianas: ácido hexadecanoico, éster metílico, 17-pentatriaconteno, dasycarpidan-1-metanol e acetato (éster). Entretanto, o ME de S. tenerrimum exibiu melhor efeito antibacteriano do que o PEE devido à presença dos compostos bioativos ácido 1,2-benzenodicarboxílico, éster diisooctil, tetratetracontano, 1-docosene, 1,2-benzoenodiol e ácido benzoico. Assim, moléculas antibacterianas promissoras podem ser isoladas de S. tenerrimum para melhor uso terapêutico.

Spectral analysis and Antibacterial activity of the bioactive principles of Sargassum tenerrimum J. Agardh collected from the Red sea, Jazan, Kingdom of Saudi Arabia

Abstract Seaweeds are a major marine resource that can be explored to develop novel pharmaceutical molecules. The present study showed the presence of unique bioactive components in the petroleum ether extract (PEE) and methanolic extract (ME) of Sargassum tenerrimum. The gas chromatography-mass spectrometry analysis suggested that the PEE of S. tenerrimum contained antibacterial biomolecules: hexadecanoic acid, methyl ester, 17-pentatriacontene, dasycarpidan-1-methanol, and acetate (ester). However, the ME of S. tenerrimum exhibited better antibacterial effect than the PEE due to the presence of the bioactive compounds 1,2-benzenedicarboxylic acid, diisooctyl ester, tetratetracontane, 1-docosene, 1,2-benzenediol, and benzoic acid. Thus, promising antibacterial molecules can be isolated from S. tenerrimum for better therapeutic use.

Resumo As algas marinhas são um importante recurso marinho que pode ser explorado para desenvolver novas moléculas farmacêuticas. O presente estudo mostrou a presença de componentes bioativos únicos no extrato etéreo de petróleo (PEE) e no extrato metanólico (ME) de Sargassum tenerrimum. A análise por cromatografia gasosa-espectrometria de massa sugeriu que o PEE de S. tenerrimum continha biomoléculas antibacterianas: ácido hexadecanoico, éster metílico, 17-pentatriaconteno, dasycarpidan-1-metanol e acetato (éster). Entretanto, o ME de S. tenerrimum exibiu melhor efeito antibacteriano do que o PEE devido à presença dos compostos bioativos ácido 1,2-benzenodicarboxílico, éster diisooctil, tetratetracontano, 1-docosene, 1,2-benzoenodiol e ácido benzoico. Assim, moléculas antibacterianas promissoras podem ser isoladas de S. tenerrimum para melhor uso terapêutico.

Spectral analysis and Antibacterial activity of the bioactive principles of Sargassum tenerrimum J. Agardh collected from the Red sea, Jazan, Kingdom of Saudi Arabia / Análise espectral e atividade antibacteriana dos princípios bioativos de Sargassum tenerrimum J. Agardh coletados no mar Vermelho, Jazan, Reino da Arábia Saudita

Abstract Seaweeds are a major marine resource that can be explored to develop novel pharmaceutical molecules. The present study showed the presence of unique bioactive components in the petroleum ether extract (PEE) and methanolic extract (ME) of Sargassum tenerrimum. The gas chromatography-mass spectrometry analysis suggested that the PEE of S. tenerrimum contained antibacterial biomolecules: hexadecanoic acid, methyl ester, 17-pentatriacontene, dasycarpidan-1-methanol, and acetate (ester). However, the ME of S. tenerrimum exhibited better antibacterial effect than the PEE due to the presence of the bioactive compounds 1,2-benzenedicarboxylic acid, diisooctyl ester, tetratetracontane, 1-docosene, 1,2-benzenediol, and benzoic acid. Thus, promising antibacterial molecules can be isolated from S. tenerrimum for better therapeutic use.

Resumo As algas marinhas são um importante recurso marinho que pode ser explorado para desenvolver novas moléculas farmacêuticas. O presente estudo mostrou a presença de componentes bioativos únicos no extrato etéreo de petróleo (PEE) e no extrato metanólico (ME) de Sargassum tenerrimum. A análise por cromatografia gasosa-espectrometria de massa sugeriu que o PEE de S. tenerrimum continha biomoléculas antibacterianas: ácido hexadecanoico, éster metílico, 17-pentatriaconteno, dasycarpidan-1-metanol e acetato (éster). Entretanto, o ME de S. tenerrimum exibiu melhor efeito antibacteriano do que o PEE devido à presença dos compostos bioativos ácido 1,2-benzenodicarboxílico, éster diisooctil, tetratetracontano, 1-docosene, 1,2-benzoenodiol e ácido benzoico. Assim, moléculas antibacterianas promissoras podem ser isoladas de S. tenerrimum para melhor uso terapêutico.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Spectral analysis and Antibacterial activity of the bioactive principles of Sargassum tenerrimum J. Agardh collected from the Red sea, Jazan, Kingdom of Saudi Arabia.

Seaweeds are a major marine resource that can be explored to develop novel pharmaceutical molecules. The present study showed the presence of unique bioactive components in the petroleum ether extract (PEE) and methanolic extract (ME) of Sargassum tenerrimum. The gas chromatography-mass spectrometry analysis suggested that the PEE of S. tenerrimum contained antibacterial biomolecules: hexadecanoic acid, methyl ester, 17-pentatriacontene, dasycarpidan-1-methanol, and acetate (ester). However, the ME of S. tenerrimum exhibited better antibacterial effect than the PEE due to the presence of the bioactive compounds 1,2-benzenedicarboxylic acid, diisooctyl ester, tetratetracontane, 1-docosene, 1,2-benzenediol, and benzoic acid. Thus, promising antibacterial molecules can be isolated from S. tenerrimum for better therapeutic use.

Icariin attenuates isoproterenol-induced cardiac toxicity in Wistar rats via modulating cGMP level and NF-κB signaling cascade.

Icariin, a major component of Epimedium species, was evaluated using isoproterenol (ISO)-induced cardiotoxicity in Wistar rats. Rats were treated with icariin at the doses of 1, 5, and 10 mg kg-1 orally for 15 days. Afterward, rats were administered with ISO (85 mg kg-1, subcutaneous) on 14th and 15th day to produce cardiac injury. Sildenafil (0.7 mg kg-1, intraperitoneal) was used as a positive reference to compare the effects of icariin. ISO-treated rats showed significant changes in hemodynamic parameters. Elevated levels of cardiac troponin T, nitric oxide, and tumor necrosis factor-alpha in serum, positive expression of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase in cardiac tissue, and a decrease in serum level of interleukin-10, manifested inflammation and associated cardiac injury. However, pretreatment with icariin and sildenafil significantly prevented the hemodynamic fall and showed improved contractile and lusitropic states. Furthermore, pretreatment groups also showed a reversal of other toxicity markers to normal. Additionally, pretreatment with icariin and sildenafil significantly increased the myocardial cyclic guanosine monophosphate (cGMP) levels. Our results thus indicated the potential role of icariin in the restoration of the ISO-induced cardiac toxicity and restored membrane integrity through modulation of cGMP and NF-κB signaling.

Diastolic dysfunction grading, echocardiographic and electrocardiogram findings in 50 patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG). METHODS: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation. RESULTS: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21). CONCLUSION: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

Amyloid beta (Aß) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aß peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aß1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aß1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aß1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aß1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro.

BACKGROUND: Many inflammatory responses including chemotaxis, production of nitric oxide, and modulation of pro-inflammatory cytokines in immunological cells are mediated by p38MAPK. Due to its pivotal role, p38MAPK has been extensively explored as a molecular target for inhibition of chronic inflammation; however, it has not been successful so far due to serious toxicity issues. Among several downstream substrates of p38, mitogen-activated protein kinase-activated protein kinase 2 (MK2) has been reported to be a direct and essential downstream component in regulation of innate immune and inflammatory responses. Thus, in this study, we aimed to understand relative molecular differences between p38 and MK2 kinase inhibition in terms of a comparative anti-inflammatory potential along with molecular regulation of toxicity biomarkers such as Phospho c-Jun N-Terminal Kinase (pJNK), caspase-3, and hepatic enzyme levels in relevant human cells in vitro. RESULTS: Both p38 and MK2 inhibitors attenuated lipopolysaccharide-induced pro-inflammatory biomarkers expression. In addition, both these kinase inhibitors inhibited release of Th1 and Th17 cytokines in phytohemagglutinin-induced cells with MK2 inhibitor showing a better potency for inhibition of Th1 cytokine release, interferon-γ. In the mechanistic differentiation studies, p38 inhibitors displayed an increase in pJNK and caspase-3 activity in U937 cells and elevation in aspartate transaminase enzyme in HepG2 cells, whereas MK2 inhibitor did not show such adverse toxic effects. CONCLUSION: Taken together, inhibition of MK2 kinase can be a relatively preferred strategy as an anti-inflammatory therapy over direct inhibition of p38 kinase in p38MAPK pathway.

Protective Effect of Irbesartan an Angiotensin (AT1) Receptor Antagonist in Unpredictable Chronic Mild Stress Induced Depression in Mice.

Objective: Oxidative stress and alternation of renin-angiotensin system has been implicated in the pathophysiology of various cardio vascular, endocrine including mood and anxiety disorders. The present study evaluated the role of irbesartan in stress induced different models of depression. Materials and method: Mice were treated with irbesartan (40 mg/kg), fluoxetine (25 mg/kg) alone in combination orally. Drugs treatment started after 2 weeks from the beginning of the unpredictable mild stress (UCMS) protocol. Behavioural tests were performed on week 6, at least 24 h after the last treatment. Modified forced swim test (MFST), tail suspension test (TST) and open field test (OFT) were used followed by antioxidant markers and 5-HT levels determination. Result: Irbesartan increased swimming, climbing and decreased immobility times in MFST, decrease immobility time in TST. Irbesartan also increased no. of field crossings; rearings and also increased time spent in the centre of OFT. Thus, antidepressant like activity in UCMS mice was observed. Combination of irbesartan with fluoxetine showed potentiating effect of behavioural parameters in all animal models. Combination groups also showed antioxidant effects and elevated the 5-HT levels in UCMS mice. Conclusion: Chronic administration of Irbesartan exerted antidepressant like effect, reduced oxidative stress and elevated brain 5-HT levels.

Protective Effect of Guggulipid in High Fat Diet and Middle Cerebral Artery Occlusion (MCAO) Induced Ischemic Cerebral Injury in Rats.

AIM: The role of guggulipid was evaluated in high fat diet and middle cerebral artery occlusion (MCAO) induced ischemic cerebral dysfunctions in rats of either sex. MATERIALS AND METHODS: Ethyl acetate extract of guggul known as guggulipid was prepared and administered to rats. Animals were divided into 9 groups, consisting 6 rats, each receiving different treatments per orally for 8 weeks. Control group rats received normal control diet while rest of the other groups animals were fed high fat diet (HFD) for 8 weeks. Cerebral ischemia was induced for 2 h followed by reperfusion for 22 h. Locomotor activity and grip strength tests were performed immediately after 24 h of reperfusion followed by biochemical estimations and histopathology. RESULTS: Locomotor activity and grip strength were significantly decreased in HFD and HFD fed MCAO groups and improved significantly in pretreatment groups. Cerebral infarction, thiobarbituric acid reactive substances (TBARs), nitric oxide and tumor necrosis factor alfa (TNFα) levels were increased, pretreatment of guggulipid alone and with aspirin significantly reduced these markers. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase, levels were decreased but all drug pretreated groups showed significant improvement in those markers. CONCLUSION: Guggulipid demonstrated neuroprotection owing to its hypolipidemic, antioxidant, anti-inflammatory and anti-thrombotic activities but further research is warranted to confirm its role in cerebral ischemia.

Histamine H3 Receptor Agonist Imetit Attenuated Isoproterenol Induced Renin Angiotensin System and Sympathetic Nervous System Overactivity in Myocardial Infarction of Rats.

BACKGROUND: Myocardial infarction is an alarming health issue, needs great attention. The present study investigated the role of histamine-H3 receptor (H3R) agonist imetit in relationship to sympathetic and renin angiotensin system in Wistar rats. MATERIALS AND METHODS: Subcutaneous injection of isoproterenol (85 mg/kg) on last 2 consecutive days in per se group and 7 days treatment of different groups at 24 h interval induced myocardial infarction in Wistar rats. H3R agonist imetit (10 mg/kg), H3R antagonist thioperamide (5 mg/kg), losartan (10 mg/kg) were administered orally to evaluate imetit's cardioprotective potential effect by measuring plasma cardiac antioxidant markers, angiotensin II, norepinephrine levels and histopathological analysis. RESULTS: Isoproterenol significantly elevated the angiotensin II and norepinephrine levels in rat plasma. This study revealed that pre-treatment with imetit similar to losartan attenuated norepinephrine and angiotensin II levels whereas thioperamide showed its antagonistic effect by diminishing imetit's effects. Furthermore, its protective effect was confirmed by restoration of cardiac antioxidant markers and histopathological improvement of myocardium integrity. CONCLUSION: This study confirm imetit's cardioprotective potential and also reveals renin angiotensin system, sympathetic system and H3R correlation in isoproterenol induced toxicity in rats. However, molecular studies must be warranted to prove the role of H3R in myocardial infarction.

Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats.

The present study was carried out to evaluate whether the combined administration of sarcosine with risperidone possess any advantageous effects on dopaminergic and NMDA receptor-mediated glutamatergic neurotransmissions as compared to single drug administration in rats. The Wistar rats were divided into 7 groups each with different treatments. MK-801 (0.1 mg/kg, i.p.) was injected as single dose on 14th day for inducing learning and memory deficits in animals. Sarcosine (300 and 600 mg/kg, i.p.) and risperidone (0.2 mg/kg, i.p.) were administered daily for 14 days. Spatial habituation learning and hole board tests were performed on 14th day followed by measurement of GABA and 5-HT levels in brain tissues of rats. Pretreatment of sarcosine (600 mg/kg, i.p.) non-significantly improved learning and memory deficits induced by non-competitive NMDA receptor antagonist MK-801, significantly increased the GABA and decreased the 5-HT levels (p<0.05). Combined administration of sarcosine (300 mg/kg, i.p.) with risperidone (0.1 mg/kg, i.p.) synergistically improved cognitive deficits significantly, decreased % errors in hole board learning test, and increased centre time, corner time in spatial habituation learning test (p<0.05). The combined administration also potentiated the GABA and decreased 5-HT levels, indicating that the increased synaptic glycine concentrations may enhance NMDA receptor function which is directly linked with increased GABAergic transmission in striatum region and decreased 5-HT levels showed antagonistic action hence, enhancing the cognition. Our results suggest that combined administration of sarcosine with risperidone may strengthen glutamatergic tone in striatum. Thus, it may be a novel regime to improve psychotic symptoms and cognitive deficit in schizophrenia.

Antidepressant Effect of Thymoquinone in Animal Models of Depression.

OBJECTIVE: The present study was carried out to determine the role of thymoquinone (TQ) in modulating the levels of neurotransmitter and reducing the oxidative stress in animal models of depression. MATERIAL AND METHODS: Mice were divided into 5 groups, each group had 6 animals. TQ (20 mg/kg) in corn oil and fluoxetine (10 mg/kg) in normal saline were administered intraperitoneally (i.p.) half an hour before performing behavioural tests. Modified forced swim test (MFST) and tail suspension test (TST) were used to assess the antidepressant effect in mice. Animals were sacrificed and their brains were removed for biochemical estimation after performing behavioural tests. RESULTS: TQ treatment showed increased swimming, climbing and decreased immobility times in MFST and TST. Combination of TQ with fluoxetine in MFST and TST showed potentiating effect in the present study. A significant elevation of 5-hydroxytryptamine (5-HT) levels was observed following TQ administration in the behavioural models studied. MFST and TST reduced glutathione and elevated TBARS levels in mice. Pre-treatment of TQ restored glutathione and decreased TBARS levels. TQ combination with fluoxetine also showed reduction of TBARS and increased glutathione levels. CONCLUSION: TQ demonstrated antidepressant effects in MFST and TST respectively in the present study. It further demonstrated antioxidant effects by reducing thiobarbituric acid reactive substance (TBARS) and increasing reduced glutathione (GSH) levels. Although our results are preliminary, further investigations may be required however, based on afore mentioned results, it may be suggested that TQ could be a potential candidate for the management of depression.

A prospective research study of anti-glaucoma drugs prescribing, utilization pattern and adverse drug reaction recording in a university hospital.

OBJECTIVE: This study was carried out to evaluate the drug prescribing, utilization pattern and adverse drug reactions recording associated with drugs prescribed to glaucoma patients. MATERIALS AND METHODS: A total of 50 glaucoma patients were included in the study, based on inclusion and exclusion criteria. All the observations were recorded in drug utilization and ADR recording documentation form. RESULTS: Out of 50 patients suffering from glaucoma, 38 patients (76%) were diagnosed open angle glaucoma, 4 patients (8%) closed angle glaucoma and 8 patients (16%) post-operative respectively. There were 19 patients (38%) males and 31 patients (62%) were females. The age range between 41-50 years had the maximum number of patients 15 (30%). A total of 17 patients (34%) had family history of glaucoma. Timolol was prescribed to 34 patients (68%), followed by dorzolamide 18 patients (36%) and acetazolamide 14 patients (28%). A total of 32 patients (64%) were prescribed single drug therapy whereas 18 patients (36%) were on multiple drug therapy. A total of 25 patients (50%) reported ADR. In the present study, latanoprost was associated with maximum number of ADRs 9 patients (18%) followed by acetazolamide 7 patients (14%), dorzolamide 4 patients (8%), then timolol 3 patients (6%) and pilocarpine 2 patients (4%). According to Naranjo scale, in 6 patients (24%) the ADR were unlikely, 12 patients (48%) were given possible score, 3 patients (12%) were given probable score, and 4 patients (16%) were given definite scores. CONCLUSION: In the present study, the maximum patients were in the age group of 41-50 years. The most commonly prescribed drugs were timolol followed by dorzolamide, acetazolamide. Latanoprost was associated with maximum number of ADRs.

Monoterpene phenolic compound thymol prevents high fat diet induced obesity in murine model.

CONTEXT: Obesity has become a worldwide health problem. Most of the synthetic anti-obesity drugs have failed to manage the obesity due to either ineffectiveness or adverse effect. The research of prominent chemical constituents from herbal for the management of obesity has greatly increased. OBJECTIVE: The main objective of the present study was intended to examine the effects of thymol in high-fat diet (HFD)-induced obesity in murine model. METHODS: Male Wistar rats were fed HFD for 6 weeks to induce obesity. Thymol (14 mg/kg) administered orally twice a day to HFD-fed rats for 4 weeks. Alteration in body weight gain, visceral fat-pads weight and serum biochemical markers were assessed. RESULTS: At the end of study, rats fed with HFD exhibited significantly (p < 0.001) enhanced body weight gain, visceral pad weight, lipids, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), glucose, insulin and leptin levels compared with rats fed with normal diets. Thymol treatment showed significantly (p < 0.001) decreased body weight gain, visceral fat-pad weights, lipids, ALT, AST, LDH, BUN, glucose, insulin, and leptin levels in HFD-induced obese rats. Furthermore, thymol treatment showed significantly decreased serum lipid peroxidation and increased antioxidant levels in HFD-induced obese rats. DISCUSSION AND CONCLUSIONS: Thymol prevents HFD-induced obesity in murine model through several mechanisms including attenuation of visceral fat accumulation, lipid lowering action, improvement of insulin and leptin sensitivity and enhanced antioxidant potential.

Okadaic acid-induced Tau phosphorylation in rat brain: role of NMDA receptor.

Okadaic acid (OKA) is a potent inhibitor of protein phosphatases 1/2A (PP2A). Inhibition of PP2A leads to hyperphosphorylation of Tau protein. Hyperphosphorylated Tau protein is present in intraneuronal neurofibrillary tangles a characteristic feature of neuropathology of Alzheimer's disease. Intracerebroventricular (ICV) administration of OKA causes neurotoxicity, which is associated with increased intracellular Ca(2+) level, oxidative stress, and mitochondrial dysfunction in the brain areas. The present study explored Tau phosphorylation in OKA-treated rats in relation to memory function, PP2A activity, intracellular Ca(2+), glycogen synthase kinase-3ß (GSK-3ß) and N-methyl-d-aspartate (NMDA) receptor after 13days of OKA (200ng, ICV) administration in rats, memory was found impaired in the water maze test. OKA-induced memory-impaired rats showed increased mRNA and protein expression of Tau, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), Calpain and GSK3ß in the hippocampus and cerebral cortex. On the other hand, mRNA expression and activity of PP2A was reduced in these brain areas. OKA treatment also, resulted in decrease in mRNA expression of C and N terminals of Tau. Treatment with NMDA antagonist, MK801 (0.05mg/kg, i.p.) for 13days significantly prevented OKA-induced changes in the expression of PP2A, Tau, GSK3ß, CaMKII and Calpain. Further, daily administration of anticholinergic drug, donepezil (5mg/kg, p.o.), and the NMDA receptor antagonist, memantine (10mg/kg, p.o.) initiated after OKA administration for 13days significantly attenuated OKA-induced variation in Tau, Tau-C terminal, Tau-N terminal CaMKII, Calpain, PP2A and GSK3ß. These results infer that NMDA antagonist MK801 and memantine are effective against OKA-induced neurotoxicity. Therefore, the present study clearly indicates the involvement of NMDA receptor in OKA (ICV)-induced Tau hyperphosphorylation.