Drug Of First Choice Research Articles

New WHO guidelines for treating rhodesiense human African trypanosomiasis: expanded indications for fexinidazole and pentamidine.

Human African trypanosomiasis is a neglected tropical disease that is usually fatal without treatment. WHO has revised its rhodesiense human African trypanosomiasis treatment guidelines on the basis of an independent systematic literature review and following the GRADE methodology. This Review reports on the decision-making process and summarises the new recommendations and their potential implications for health-care professionals and policy makers. Due to data scarcity, all recommendations are conditional and based on very low certainty of evidence. Fexinidazole replaces suramin and melarsoprol as the first-line therapy in individuals aged 6 years and older with a bodyweight of 20 kg or more. As fexinidazole is effective in both stages of rhodesiense human African trypanosomiasis, a lumbar puncture for staging is no longer required. In settings in which first-choice drugs are not readily available, immediate interim treatment with pentamidine is suggested. The introduction of oral fexinidazole represents an advancement in the management of rhodesiense human African trypanosomiasis considering the life-threatening adverse reactions individuals can have to melarsoprol. However, children below the age or weight limits remain ineligible for treatment with fexinidazole.

Synthesis, Molecular Docking Studies and Biological Evaluation of N-(α-Benzamido Cinnamoyl) Piperonal Hydrazones

Background: Nowadays, inflammation is recognized as the underlying cause of a number of diseases, but NSAIDs are the first drug of choice, having several side effects. Additionally, excessive cellular oxidative stress is often considered a major contributor to pathophysiological conditions, the development of cancer, and other diseases. Antimicrobial resistance is a global concern, hence, there is a critical need for the development of novel therapeutic agents to fight the emergence and increasing prevalence of resistant pathogens. This creates an initiation to introduce new molecules which act as efficient therapeutic agents with diminished side effects. Objective: As a part of our search for newer agents with enhanced activity profiles, it was planned to synthesize novel 2- (benzamido)-N-((benzo[d][1,3]dioxol-4-yl)methylene)-3-(substituted phenyl) acrylohydrazides and to investigate them for antiinflammatory, antioxidant, cytotoxic, antimicrobial activities. Furthermore, in silico studies were performed for title compounds to predict molecular properties, bioavailability, drug-likeness, and bioactivity scores, molecular docking studies were also performed against biological targets. Methods: The title compounds 1-14 were synthesized by nucleophilic addition of piperonal in ethanol, few drops of acetic acid to the intermediate 2-(benzamido)-3-(aryl)acrylohydrazides. The title compounds were tested for their antiinflammatory activity by in vivo carrageenan-induced rat paw edema method, in vitro COX-2 inhibition assay; in vitro cytotoxic activity evaluation by MTT assay; antioxidant activity by Lipid peroxidation, DPPH assay, Nitric Oxide scavenging assay and Hydrogen peroxide scavenging assay; and antimicrobial activity by cup plate method. Physicochemical properties and bioactive scores of title compounds were evaluated by in silico studies. Molecular docking studies were carried out for the title compounds against COX-2 (PDB: 5F19) and EGFR (PDB:1XKK). Results: Among the series, 4-Hydroxy-3,5-dimethoxy derivative (5) displayed good anti-inflammatory and antioxidant activities; Vanillinyl derivative (4) displayed good cytotoxicity and antimicrobial activity when compared to that of the respective standards. Compounds 5 & 4 also exhibited good docking scores with COX-2 and EGFR, respectively. All title compounds obeyed Lipinski’s rule of five and also exhibited acceptable molecular properties, drug-likeness properties, and moderate to good bioactivity scores in in silico studies. Conclusion: The study suggested that the title compounds showed notable pharmacological properties, could emerge as lead compounds, and be further explored as promising therapeutic agents.

Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: A randomized controlled trial

BackgroundCutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1β play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. MethodsIn this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA. ResultsThe cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29. ConclusionrSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time. Clinical trials registrationClinicalTrial.gov under NCT06000514.

Comparison of Mutant Prevention Concentrations of Fluoroquinolones Against ESBL-Positive and ESBL-Negative Klebsiella pneumoniae Isolates from Orthopedic Patients.

The majority of Klebsiella pneumonia isolates possess the extended-spectrum beta-lactamase (ESBL) enzymes. Therefore, K. pneumoniae can easily develop drug resistance. How to effectively overcome the problem of drug resistance in K. pneumoniae is still a research hotspot. This study aimed to compare the mutant prevention concentration (MPC) of ESBL-positive and ESBL-negative K. pneumoniae isolated from orthopedic patients, which may provide a basis for the effective use of drugs to control the enrichment of resistance mutants of K. pneumoniae. The MPC90 values of 55 isolates of ESBL-positive K. pneumoniae against 4 fluoroquinolones were 32 µg/mL for levofloxacin and gatifloxacin, 16 µg/mL for ciprofloxacin, and 4 µg/mL for gemifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin and 2 for gemifloxacin and gatifloxacin, respectively. For ESBL-negative K. pneumoniae isolates, the MPC90 values were 16 µg/mL for levofloxacin and ciprofloxacin, 4 µg/mL for gemifloxacin, and 32 µg/mL for gatifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin, 2 for gemifloxacin, and 4 for gatifloxacin. For the ESBL-positive K. pneumoniae, the %T>MIC90 order was gemifloxacin > levofloxacin > ciprofloxacin > gatifloxacin. For the ESBL-negative K. pneumoniae, the %T>MIC90 order was levofloxacin > gemifloxacin > ciprofloxacin > gatifloxacin. The mutant-preventing ability of gatifloxacin and gemifloxacin was the strongest among the 4 fluoroquinolones. So gemifloxacin may be the first choice of drug to treat K. pneumoniae infection.

Innovative approaches to assessing risk factors, diagnostics and treatment of neonatal thrombosis

Compared to children of other ages, neonates especially seriously ill and premature subjects comprise a high thrombotic risk group. A decline in the incidence of neonatal thrombosis may be accounted for by improved treatment of severe conditions in newborns and increased survival of premature infants. Neonatal and adult hemostasis exhibit distinct physiological features: difference in concentration, synthesis rate of blood coagulation factors, metabolic rate, thrombin and plasmin levels. At the same time, neonatal threshold values for natural blood coagulation inhibitors (protein C, protein S, antithrombin, heparin cofactor II) and vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) are quite low, whereas that of FVIII and von Willebrand factor exceeds those found in adults. Thus, newborns have lower plasma fibrinolytic activity. The main risk factors for developing thrombotic complications are as follows: central venous catheters, altered body fluid volume, liver disease, as well as sepsis and inflammatory processes particularly COVID-19. The significance of congenital and acquired maternal and neonatal thrombophilia may pose an additional risk factor for thrombotic complications. Low-molecular weight heparins are the first-choice drugs in treatment and prevention of neonatal thrombosis.

Frequency of Hematological Response in Patients with Chronic Myeloid Leukemia (Chronic Phase) with Imatinib After Three Months Presenting to CMH Rawalpindi

Objective: To find the frequency of haematological response in patients of chronic myeloid leukaemia (Chronic Phase) after three months of Imatinib Mesylate therapy, presenting to CMH Rawalpindi Study Design: Cross-sectional study. Place and Duration of Study: Department of Oncology Combined Military Hospital, Rawalpindi Pakistan, from Jan to Jun 2020. Methodology: Forty-six patients aged 18 and above within the chronic phase of CML were included. Patients underwent detailed clinical history, examination, baseline investigations, and bone marrow studies at presentation. Enrolled patients were given 400mg of Imatinib, and a complete haematological response was noted at the end of 3 months of therapy. Results: In our study, the age of patients ranged from 18 to 67 years, with a mean age of 47.2+10.6 years. 33(71.7%)were male, and 13(28.3%) were female. 42(91.3%) patients achieved complete haematological response to Imatinib at three months of therapy. Adverse drug reactions exhibited were oedema 18(39.1%), gastrointestinal disturbance 12(26.1%), anaemia 05(10.9%), and skin reactions 03(6.5%). Conclusion: This study has concluded that Imatinib Mesylate is highly effective in treating chronic phase CML at the haematological level and can be considered the drug of first choice in CML-CP.

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats

BackgroundVortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.MethodsThe experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.ResultsInterestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.ConclusionThus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Evaluation of multidrug resistance in tumors using 99mTc-doxorubicin

Doxorubicin (DOX) is a potent chemotherapeutic agent used as the first-choice drug in treating different types of cancer, such as leukemia, lymphoma, and breast cancer, among others. However, the development of multidrug resistance represents a significant obstacle to the successful treatment of tumors. In this study, we assessed whether labeled DOX could be uptaken by susceptible and multidrug-resistant cell lines and by tumors in vivo in animals. The efficiency of DOX labeling was maintained at around 90% in this work. To evaluate the effect of 99mTc-DOX on cells expressing active P-glycoprotein (Pgp), we utilized cultured human chronic myeloid leukemia K562 cells and the resistant counterpart Lucena 1 cells. Lucena 1 cell line showed overexpression of Pgp that was not observed in K562. Our results suggested that the resistance to labeled or unlabeled DOX can be reversed by Pgp inhibition and can be easily detected. In conclusion, administering 99mTc-DOX into mice enables the differentiation between multidrug-resistant tumors in a non-invasive way and the evaluation of tumor resistance and possible chemosensitizers.

Silibinin's Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model.

Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed to investigate the antioxidant and hepatoprotective effects of silibinin (SIL, natural agent) against MTX-induced hepatotoxicity in an adjuvant-induced arthritis (AIA) rat model. Arthritic rats were treated with SIL (100 mg/kg) and/or methotrexate (2 mg/kg). Non-arthritic rats, arthritic untreated rats, and arthritic rats who received the vehicle were followed in parallel. SIL alleviated the systemic consequences of arthritis by restoring lost weight, decreasing the erythrocyte sedimentation rate, and ameliorating joint damage, which was evident both micro- and macroscopically. Additionally, SIL prevented the histopathological alterations in the liver and significantly reduced the liver damage caused by MTX and AIA, as shown by a decrease in the markers of liver damage (ALT and AST). Furthermore, SIL relieved the oxidative stress induced by AIA and MTX in liver tissue by decreasing the lipid peroxidation (MDA) levels and enhancing the antioxidant defense system (GSH levels; catalase and superoxide dismutase (SOD) activities). In conclusion, our results suggest that SIL is a potent antioxidant and hepatoprotective agent in arthritic rats. It markedly attenuated the progression and severity of the arthritic disease and eased the oxidative stress in liver tissue by improving the pro-oxidant/antioxidant balance.

Studying the Blood Trough Level of Tacrolimus on Patients after Kidney Transplant at the Uronephreulogical Department, Bach Mai Hospital, Vietnam

Tacrolimus, a calcineurin inhibitor, is a first-choice drug for the anti-rejection treatment regimen after kidney transplantation. The daily adjusted Tacrolimus dose by therapeutic drug monitoring is essential for patients to achieve optimal effects and minimize complications. We conducted a retrospective analysis of 70 kidney transplant patients at Bach Mai Hospital from January 2019 to the end of June 2020 to monitor changes in the blood trough level of Tacrolimus over time and analyze some risk factors affecting the blood trough level of Tacrolimus after a kidney transplant. Total whole-blood samples were collected at 6 time points: pre-transplant, on transplant day, and the 1st, 2nd, 4th, and 8th day after surgery. During the study, we recorded 4 cases with accelerated acute rejection with the blood trough level of Tacrolimus on the first day after transplantation of 5.325 ± 1.531 ng/mL and lower than the medium level in the remaining group of patients 10.371 ± 4.550 ng/mL at the same time (p = 0.031). There was no significant difference between the two groups of patients in age, gender, BMI, chronic disease status (hypertension, hepatitis C, type 2 diabetes), pre-transplant blood urea, and serum creatinine concentrations. These characteristics were included in the linear regression models which affected the blood trough level of Tacrolimus. This showed that none of the above risk factors had a significant effect on the blood trough level of Tacrolimus on the first day after transplantation (p &gt; 0.05).&#x0D; &#x0D;

Migraine treatment – updated recommendations 2024 –development of the Expert Group of the Headache Section ofthe Polish Neurological Society and the Polish Society for theStudy of Pain

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients qualityof life. Migraine treatment recommendations are provided based on a review of the literature from randomizedclinical trials and the consensus of a national expert panel. All available medical reference systems were screened for the range of past and present clinical studies on migraine with and without aura and on migraine-like syndromes.The results of these studies were presented in accordance with the recommendations of the Migraine Section ofthe Polish Neurological Society and the Polish Society for the Study of Pain. For the acute treatment of migraineattacks, oral non-steroidal antiinflammatory drug (NSAID), triptans and new class of drugs gepants and ditans arerecommended. The administration should follow the concept of stratified treatment. Before intake of NSAID andtriptans, oral metoclopramide is recommended. In very severe attacks, subcutaneous sumatriptan are drugs of firstchoice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful. Forthe prophylaxis of migraine, old and new drugs – betablockers flunarizine, valproic acid, and topiramate as well asmonoclonal anti CGRP antibodies, gepants and botulin toxin are drugs of first choice.

Treatment adherence and the contemporary approach to treating type 2 diabetes mellitus.

The rising burden of type 2 diabetes mellitus (T2D) poses a significant healthcare challenge on a global scale. The economic impact is also substantial and continually increasing. In Serbia, even though the prevalence is officially around 12 percent, nearly 40 percent of the adult population is estimated to be living with undiagnosed diabetes and more than half the population is obese or overweight. This review comprehensively addresses the present approach to treating T2D, emphasizing the critical role of treatment adherence. We review the various components of T2D treatment, underlining the significance of lifestyle modifications. The pros and cons of medications used in treatment are discussed and factors influencing adherence are analysed. A healthy lifestyle remains the foundation of the treatment, and if not sufficient, early pharmacotherapy is initiated. Medications have been developed to lower blood sugar levels with cardiorenal protection, however, due to their still high cost, metformin remains the drug of first choice for most patients. Adherence to the treatment regimen is often poor. Factors associated with this are diverse and often multiple in a particular patient. Poor adherence is associated with poor glycaemic control, increased risk of disease complications, higher cardiovascular risk, increased mortality, hospitalizations, and healthcare costs. In addition to reducing the complexity of drug therapy and better informing the patient, improved education and motivation could lead to greater adherence. Enhanced communication between the patient and the physician and reduced treatment costs could also have a positive impact. The review concludes that addressing factors affecting adherence can significantly improve T2D outcomes and reduce costs. Further research is needed to identify region-specific risk factors for poor adherence.

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome.

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia-reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase-MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.

Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 μM and ≤ 41 μM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 μM), 1e (IC50 4.8 μM), and 1i (IC50 5.2 μM) exhibited potencies equivalent to MTZ (IC50 4.9 μM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 μM) and 48 h (IC50 2.1 μM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 μM) or low cytotoxicity (CC50 between 69 and 100 μM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.

Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation.

Cold injury or frostbite is a common medical condition that causes serious clinical complications including sensory abnormalities and chronic pain ultimately affecting overall well-being. Opioids are the first-choice drug for the treatment of frostbite-induced chronic pain; however, their notable side effects, including sedation, motor incoordination, respiratory depression, and drug addiction, present substantial obstacle to their clinical utility. To address this challenge, we have exploited peripheral mu-opioid receptors as potential target for the treatment of frostbite-induced chronic pain. In this study, we investigated the effect of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripheral mu-opioid receptor agonist, on frostbite injury and hypersensitivity induced by deep freeze magnet exposure in rats. Animals with frostbite injury displayed significant hypersensitivity to mechanical, thermal, and cold stimuli which was significant ameliorated on treatment with different doses of DALDA (1, 3, and 10 mg/kg) and ibuprofen (100 mg/kg). Further, molecular biology investigations unveiled heightened oxido-nitrosative stress, coupled with a notable upregulation in the expression of TRP channels (TRPA1, TRPV1, and TRPM8), glial cell activation, and neuroinflammation (TNF-α, IL-1β) in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of frostbite-injured rats. Treatment with DALDA leads to substantial reduction in TRP channels, microglial activation, and suppression of the inflammatory cascade in the ipsilateral L4-L5 DRG and spinal cord of rats. Overall, findings from the present study suggest that activation of peripheral mu-opioid receptors mitigates chronic pain in rats by modulating the expression of TRP channels and suppressing glial cell activation and neuroinflammation.

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP&amp;lt;5 mg/L and FC&amp;lt;250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

A rapid-floating natural polysaccharide gel–raft with double-effect for the treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.

Pharmacological therapy in the management of temporomandibular disorders and orofacial pain: a systematic review and meta-analysis

BackgroundTemporomandibular disorders (TMD) are manifested by soreness in the jaw joint area and jaw muscles, clicks or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or speaks. Several classes of drugs are used to treat symptoms. This review aims to assess which drug suits the different signs.MethodsPubmed, Web of Science and Lilacs were systematically searched until 01/02/2023. Clinical trials were selected that dealt with drugs used in temporomandibular dysfunctionResultsOut of 830 papers, eight studies were included. The Meta-Analysis with Continuous Outcomes with Pre-Calculated Effect Sizes resulted in the rejection that there is intergroup variability (p.0.74).ConclusionsTreatment of orofacial pain is still a significant challenge for dentistry. We can conclude that there is no drug of first choice in the treatment of temporomandibular pain. However, the clinician must distinguish the type of pain and the aetioloic cause of the pain so that the patient can be treated and managed pharmacologically.

Clinical Importance of Agrya Ausadha Aragvadha in the Management of Vicharchika: A Pharmacological Review

In Ayurvedic clinical practice, agrya ausadha are the first drug of choice for treatment of various diseases. Aragvadha, as an agrya ausadha, is employed for its therapeutic benefits in both internal and external applications. It is notably used for mridu virechana (mild purgation) and as a topical remedy for various types of Kustha. In ayurvedic dermatology kustha has been taken as supreme word for all skin diseases. Vicharchika, classified as a Kshudra Kustha, is treated through the dual principles of Sodhana (purification) and Samana Chikitsa (pacification). The Majja (pulp) of Aragvadha is utilized for internal Sodhana therapy, while the leaves are applied externally as a paste for samana Chikitsa. Preliminary findings indicate that Aragvadha meets the criteria for an ideal drug as per classical Ayurveda, given its accessibility (Bahuta), versatility in formulations (anekvidhkalpana), and effectiveness (yogatyam). Aragvadha, through its varied formulations, plays a crucial role in the Ayurvedic management of Vicharchika. Its use aligns with the principles of Sodhana and Samana Chikitsa, offering a comprehensive approach to treating this skin disorder. The study highlights the clinical significance of different parts of Aragvadha and supports its continued use in Ayurvedic dermatological practice.

Induced Ruminal Lactic Acidosis in Sheep Treated with Various Remedial Agents in Libo Kemkem Districts, Northwest Ethiopia.

Grain overload is a ruminant metabolic disorder associated with overingestion or a sudden change to rapidly fermentable concentrate feeds. A randomized clinical trial was carried out in Libo Kemkem districts to investigate vital signs, ruminal fluid, and hematological changes in sheep related to grain overload and to assess the treatment efficacy of various remedial agents in Farta sheep breeds. All sheep were selected by using the simple random process, and categorized into four groups of eight animals groups I, II, and III in which each sheep was given 80 g of wheat flour per kg of body weight then baking soda, Magnalax, and digestive powder were treated successively, but group IV was the negative control group. The current clinical trial explained that all acidotic sheep had statistically significant (p < 0.0002) lower body temperature, rumen motility, protozoa activity, and ruminal fluid pH with 38.48 ± 0.20, 0.5 ± 0.89, 6 (75%), and 5.37 ± 0.34 mean value successively. Nevertheless, there were significant (p < 0.0059) increments in hematological variables including total red blood cell, total white blood cell, packed cell volume, and hemoglobin estimation with 14.05 ± 1.27, 12.71 ± 0.99, 40.78 ± 5.24, and 14.78 ± 1.83 mean value, respectively, before treatment in acidotic sheep. There were also vital sign increments including pulse rate, respiratory rate, skin turgor, and capillary refill time with 123.5 ± 27.1, 73.75 ± 12.71, 3 ± 1.78, and 3.37 ± 1.77 mean values, respectively, before medical treatment in acidotic sheep. Digestive powder was the first drug of choice, followed by Magnalax, and baking soda was ranked at the end based on clinical recovery. The treatment effectiveness illustrated that all treatments could cure the grain overload. Nevertheless, digestive powder is the drug of choice based on the clinical and systemic recovery of the sheep. In addition to this, sheep should be introduced gradually to concentrate rations over 2-3 weeks with a mixture of concentrate in the milled feed containing roughage.