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Introduction: Brugada Syndrome (BrS) is an inherited arrhythmia syndrome characterised by ST-segment elevation in the right precordial ECG leads and is associated with an increased risk of sudden cardiac death. We identify and characterise a novel SCN3B variant encoding the regulatory β3-subunit of the cardiac voltage-gated sodium channel, Na V 1.5., Methods and Results: A 54-year-old Caucasian male presented with palpitations and dizziness. An ECG identified a spontaneous type 1 BrS pattern and review of his medical records revealed a prior type 1 BrS ECG. Next generation sequencing of a BrS risk panel of genes identified a novel SCN3B deletion (c. c412-414, p.T138Del) yielding a single amino acid deletion. No other pathogenic variants were identified. Using site-directed mutagenesis we made the β3-ΔT138 variant and examined structural and functional effects in a heterologous system. Computational predictions together with circular dichroism spectroscopy showed highly localised structural perturbations with minimal effect on the gross protein architecture. Biotinylation, co-immunoprecipitation and surface cross-linking experiments identified normal β3 surface expression and interaction with Na V 1.5. Electrophysiological analysis identified reduced peak current and channel availability. Additionally, an accelerated fast inactivation was observed only in the presence of both wild-type and ΔT138 β3-subunits, reflecting the heterozygous individual. These effects are consistent with a loss-of-function phenotype., Conclusion: A novel BrS associated SCN3B deletion introduced minimally disruptive structural perturbations to the regulatory β3-subunit of Na V 1.5, yet exerted significant electrophysiological effects. This variant highlights nuances of the Na V 1.5-β3 interaction and its role in maintaining normal cardiac excitability., Competing Interests: Declaration of competing interest None., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 56-year-old man with well-controlled human immunodeficiency virus, anxiety, depression, and hypercholesterolemia developed acute urticaria, lip angioedema, and respiratory distress after consumption of a cheeseburger, French fries, lemonade, and ibuprofen. He was evaluated in the emergency department and, during admission, developed asystole, diaphoresis, pallor, and a brief episode of posturing that was treated with two doses of epinephrine. Results of the initial workup with electrocardiogram, troponin, complete blood cell count, and comprehensive metabolic panel were normal. He was subsequently evaluated by an allergist for further recommendations.

Background: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings., Methods: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis., Results: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS., Conclusion: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children., (© The Author(s) [2020]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We investigated effects of the ryanodine receptor (RyR) modulator caffeine on Na + current (I Na ) activation and inactivation in intact loose-patch clamped murine skeletal muscle fibres subject to a double pulse procedure. I Na activation was examined using 10-ms depolarising, V 1 , steps to varying voltages 0-80 mV positive to resting membrane potential. The dependence of the subsequent, I Na inactivation on V 1 was examined by superimposed, V 2 , steps to a fixed depolarising voltage. Current-voltage activation and inactivation curves indicated that adding 0.5 and 2 mM caffeine prior to establishing the patch seal respectively produced decreased (within 1 min) and increased (after ~2 min) peak I Na followed by its recovery to pretreatment levels (after ~40 and ~30 min respectively). These changes accompanied negative shifts in the voltage dependence of I Na inactivation (within 10 min) and subsequent superimposed positive activation and inactivation shifts, following 0.5 mM caffeine challenge. In contrast, 2 mM caffeine elicited delayed negative shifts in both activation and inactivation. These effects were abrogated if caffeine was added after establishing the patch seal or with RyR block by 10 μM dantrolene. These effects precisely paralleled previous reports of persistently (~10 min) increased cytosolic [Ca 2+ ] with 0.5 mM, and an early peak rapidly succeeded by persistently reduced [Ca 2+ ] likely reflecting gradual RyR inactivation with ≥1.0 mM caffeine. The latter findings suggested inhibitory effects of even resting cytosolic [Ca 2+ ] on I Na . They suggest potentially physiologically significant negative feedback regulation of RyR activity on Na v 1.4 properties through increased or decreased local cytosolic [Ca 2+ ], Ca 2+ -calmodulin and FKBP12.

Background: Approximately 50% of patients with chronic spontaneous urticaria (CSU) experience symptoms that are not fully controlled by antihistamines, indicating an unmet clinical need., Objective: To evaluate the effects of the selective CRTh2 antagonist AZD1981 on symptoms and targeted leukocytes in adults with persistent CSU despite treatment with H1-antihistamines., Methods: We performed a single-center, randomized, placebo-controlled study involving adult CSU subjects with symptoms despite daily antihistamines. The subjects underwent a 2-week placebo run-in and 4 weeks of double-blinded therapy with either AZD1981 40 mg TID or placebo, followed by a 2-week placebo washout. The primary objective was to assess the effect of AZD1981 on CSU signs and symptoms. Secondary objectives included the effects of AZD1981 on prostaglandin D2 (PGD2)-induced eosinophil shape change, circulating leukocyte subsets, CRTh2 expression on blood leukocytes, and total blood leukocyte histamine content., Results: Twenty-eight subjects were randomized to AZD1981 or placebo, with 26 subjects completing the study. The urticaria activity scores declined during the treatment phase in both groups, and they were significantly reduced in the AZD1981 group at the end of washout. AZD1981 treatment increased circulating eosinophils and significantly impaired PGD2-mediated eosinophil shape change. CRTh2 surface expression rose significantly on blood basophils during active treatment. No serious adverse events were observed., Conclusions: This is the first study to examine the efficacy of a CRTh2 antagonist in antihistamine-refractory CSU. AZD1981 treatment was well tolerated, effectively inhibited PGD2-mediated eosinophil shape change, shifted numbers of circulating eosinophils, and reduced weekly itch scores more than hives during treatment and into washout. Further studies are needed to determine whether inhibition of the PGD2/CRTh2 pathway will be an -effective treatment for CSU., (© 2019 S. Karger AG, Basel.)

The arising cases of isoniazid-resistance have motivated research interests toward new class of molecules known as direct InhA inhibitors. Here, a combine approach of shape-based pharmacophore and descriptor-based 2D QSAR was used to identify the potential direct InhA inhibitors. The approach is duly assisted with in vitro testing and molecular dynamics simulations. A combination of empirical parameters was derived to use as a filter for cell wall permeability while 2D QSAR was used as another filter to predict the biological activity. Both filters were applied to prioritize the molecules for biological evaluation against anti-TB activity. It led to 6 potential molecules which showed > 90% inhibition of H37Rv strain of Mycobacterium tuberculosis in BACTEC assay. Further, MMGBSA binding free energy of identified molecules was compared with available highly potent molecule, 5-hexyl-2-(2-methylphenoxy) phenol (IC 50  = 5nM) using molecular dynamics simulations. It showed two molecules with comparatively higher affinity toward InhA as compared to potent molecule. It indicated the candidature of identified molecules to be further considered in anti-TB drug development pipeline.

The adherence of bacteria to epithelial cells and mucosal surfaces is a prerequisite for their colonization in the gut and a key criterion for the selection of probiotics. In this study, the eleven indigenous lactic acid bacterial isolates obtained from traditional fermented foods of Western Himalayas were screened for their adherence potential to intestinal epithelial cell lines. The level of adherence of eleven indigenous isolates to Caco-2 and HT-29 cell lines varied from 2.45 ± 0.5 to 9.55 ± 0.76% and 4.11 ± 0.68 to 12.88 ± 0.63%, respectively. Percent adhesion of indigenous isolates to Caco-2 cells was relatively lower as compared to HT-29 cells. Indigenous isolate AdF10 ( L. plantarum ) was found to be the most adhesive to HT-29 and Caco-2 with corresponding figures of 12.88 ± 0.63 and 9.55 ± 0.76%, respectively. AdF4 ( B. coagulans ) was found to be least adhesive to HT-29 and Caco-2 with respective corresponding figures of 4.11 ± 0.68 and 2.45 ± 0.5%. Based on the percent adhesion values, indigenous isolate AdF10 ( L. plantarum ) was comparable to the reference probiotic strain L. rhamnosus GG-ATCC-53103 with respective adhesion of 13.5 ± 1.19 and 10.33 ± 0.64% to HT-29 and Caco-2 cell lines. It was closely followed by indigenous isolates AdF5 ( L. plantarum ) and AdF6 ( L. plantarum ); thus, indicating their potential as a promising probiotic candidates.

Introduction: Skull fractures are traditionally classified into linear, comminuted or depressed which can either be simple or compound. A skull fracture where the bone fragment is elevated above the intact skull known as elevated skull fracture has been reported infrequently in literature., Case Presentation: We report a unique case of simple elevated vertex fracture in a 3-month-old child where the vertex had separated from the calvarium and was elevated above the level of outer table in a patient with delayed neurological deterioration. Cerebrospinal fluid leak into tight subgaleal space and gradual thrombosis of superior sagittal sinus could have led to late clinical deterioration., Conclusion: Prolonged monitoring, probably early repair of dural tear and aggressive management of raised ICP, is required. Reduction of fracture with careful manipulation of SSS should weigh the risk of exsanguination. No such case of an elevated vertex fracture has been reported so far in the literature.

This paper summarizes, elaborates upon, and contrasts the findings of two research projects that explored how general practitioners and nurses coped with the dual challenge of personal and work demands following the earthquakes in Canterbury, New Zealand, in 2010 and 2011. Qualitative data from two separate studies - the first with general practitioners and the second with nurses - are compared to identify the challenges faced during and following the earthquakes. Semi-structured interviews took place with eight general practitioners two years after the start of the earthquake sequence and 11 nurses a year later to enable exploration of the longer-term aspects of the recovery process. The interview transcripts were analyzed and coded using a constructivist grounded theory approach. The analysis identified that the earthquakes had a significant impact on nurses and general practitioners both in terms of their professional and personal lives. The nurses and general practitioners commented on the emotional impact and their support needs, as well as some of the longer-term recovery issues., (© 2016 John Wiley & Sons Australia, Ltd.)

The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 ± 23 versus 105.1 ± 12 μg/ml and SDRPL (1:1) 306.4 ± 20 versus 105.1 ± 12 μg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 ± 25 versus 54.31 ± 18 μg/ml), faster T max (two versus four hours), and enhanced area under the curve (AUC 0-∞ ) (406.92 ± 18 versus 147.72 ± 15 μg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin.

The present study was undertaken to assess the effects of potential probiotics in regulating the activity of cyclooxygenase-2 (COX-2) along with other morphological and histological analysis during 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. The rats were divided into 6 groups viz., normal control, Lactobacillus plantarum (AdF10) treated, Lactobacillus rhamnosus GG (LGG) treated, DMH treated, AdF10 + DMH treated and LGG + DMH treated. Probiotics were supplemented to rats at dose levels of 2 × 10(10) cells per day for 6 days in a week. All the treatments were continued for a period of 16 wk. DMH treatment resulted in a statistically significant increase in the levels of total sialic acid (TSA). However, on supplementation with probiotics, a significant reduction in TSA was observed. DMH treatment brought about a significant increase in the expression of COX-2. But, supplementation of probiotics brought down the protein expression to moderate level. Further, supplementation with probiotics was also able to reduce tumor incidence, tumor multiplicity and average tumor size. Therefore, treatment with probiotics has the potential of providing protection against colon cancer by suppressing the COX-2 expression as one of the protective mechanisms.

BACTEC 460 has now been phased out, so the search for an alternative is imperative. We have determined the activity of standard anti-tuberculosis drugs against intramacrophage Mycobacterium tuberculosis, in vitro, by using BACTEC 460 and MGIT 960 methods. The minimum inhibitory concentrations of isoniazid, rifampicin, ethambutol and streptomycin against intracellular M. tuberculosis H37Rv were found to be 0.2, 0.8, 8.0, and 5.0 μg/mL, respectively, by both methods. These results show a significant (p<0.001) concordance between minimum inhibitory concentrations obtained by these two different methods. MGIT 960 system uses a robust florescence quenching-based oxygen sensor, requires no radioisotope, is safe, and relatively easy to operate. Apparently, this is the first report wherein MGIT 960 has been validated for anti-tubercular susceptibility testing against intracellular M. tuberculosis H37Rv. Our preliminary data thus clearly demonstrate that the MGIT 960 method can be considered as a promising alternative to BACTEC 460 method., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.

Elevated fractures of the skull, which are rarely reported in the literature, are always compound, have maximal neurological deficits at presentation and have been reported only in adults. We report two cases of elevated skull fractures in the pediatric age group, one of which was a simple elevated fracture and presented with delayed neurological deterioration. The etiologies were a fall in first case and an animal attack (bear maul) in the second case as reported for the first time. One of the cases presented with delayed onset of left focal hemispheric signs. The first case underwent debridement, duraplasty and reduction of fracture whereas in the second case the bone flap was not replaced immediately because of gross contamination. Both patients had an excellent outcome. Elevated skull fractures are not uncommon in the pediatric age group. Compound elevated skull fractures should be managed early as open depressed fractures. Reduction of a simple elevated fracture presenting with neurological deficits not explained by any other lesion can result in a good outcome.

Apoplexy in sellar metastasis is very rare with only a few case reports in literature. A case of apoplexy in sellar metastasis from follicular thyroid carcinoma is reported and the literature is briefly reviewed. The patient presented with sudden onset headache and bi-lateral loss of vision following thyroidectomy in a case of follicular carcinoma thyroid with proven sellar metastasis. CT scan showed hyperdense blood in sellar mass suggestive of apoplexy in sellar metastasis. The patient underwent early trans-sphenoidal decompression. Apoplexy in sellar metastasis, although very rare, can be clinico-radiologically indistinguishable from pituitary apoplexy and should be especially considered in the differential diagnosis of patients with known primary neoplastic disease. In view of similar patho-physiological mechanism, sellar metastasis with apoplexy should be managed in a similar manner as pituitary apoplexy.

Acute spontaneous subdural hematoma of arterial origin, a neurosurgical emergency resulting from rupture of the perisylvian cortical artery, is a rare occurrence. We report four such patients who presented with progressive neurological deterioration. All the patients were operated and perisylvian cortical artery was identified as the source of bleeding in all the patients. Three of the patients had associated hypertension. We reviewed the clinical characteristics, etiology, and outcome of the reported cases in the literature. A high index of suspicion is necessary even in young patients in view of the phenomenon of re-rupture mimicking stroke. Early diagnosis and a wide craniotomy over the sylvian fissure to obtain hemostasis of bleeding points results in good outcome.

Background: Spinal intramedullary cysticercosis is a very uncommon manifestation of NCC, which is caused by the larvae of Taenia solium., Case Description: We report a case of spinal intramedullary cysticercosis who presented subacutely. Magnetic resonance imaging dorsal spine and CSF ELISA clinched the diagnosis. Eight weeks of medical therapy resulted in complete clinicoradiological cure., Conclusion: Surgery used to be the mainstay treatment for spinal intramedullary cysticercosis; however, early diagnosis and medical therapy with albendazole and dexamethasone can obviate the need for surgery in many patients., (Copyright 2009 Elsevier Inc. All rights reserved.)

The immunomodulatory effects of opioids are known in various infections. However, little is known about the effects of opioids in tuberculosis (TB). In the present study, we report the effects of morphine in Mycobacterium smegmatis infection in mice and macrophages. Morphine exerted a dose-dependent suppression of infection in vivo: 50 and 100 mg/kg morphine exerted significant (P<0.05) suppression whereas 5 mg/kg morphine showed no effect. Analogous to the in vivo effects, incubation of M. smegmatis-infected mouse peritoneal macrophages with morphine (100 μM) showed significant reduction in intramacrophage CFU counts. However, morphine did not show any direct antimycobacterial activity in broth dilution assay upto 100 μM concentration. Further, morphine-induced intramacrophage killing of M. smegmatis was abrogated by naloxone and aminoguanidine indicating the involvement of opioid-receptor activation and nitric oxide production in protective effects of morphine. In conclusion, morphine suppressed the progression of experimental TB in both mice and macrophage models.

Mycobacterium tuberculosis exhibits latent state due to its ability to survive for extended periods under oxygen depletion conditions. The conventional plating method employed for in vitro screening of antitubercular agents against latent state M. tuberculosis is laborious and time consuming exercise. Towards this end, BACTEC 460 TB system of antitubercular screening was evaluated for testing efficacy of antimicrobial agents in hypoxia induced model of latent tuberculosis, in vitro. In this study, drugs like isoniazid, metronidazole and rifampin were tested at concentrations- 2, 10 and 50 microg/ml for their antilatency activity by using BACTEC and conventional methods. Results obtained from both the methods were comparable (P>0.05) and a good correlation was observed between colony forming units and growth index values. Further, time to determine mycobacterial growth was significantly reduced (P

Screening of new agents for anti-tubercular activity is a challenging task due to the virulent and slow growing nature of mycobacteria. In this study, we explored the use of Mycobacterium smegmatis as an alternate model to virulent strains. We observed that the effect of standard anti-tubercular drugs was similar in mice infected with M. smegmatis and Mycobacterium tuberculosis. The total duration of the experiment, including incubation time, was 10 days in the M. smegmatis-infected mice model compared with 2 months in M. tuberculosis-infected mice. This model of anti-tubercular screening is a simple, easy to carry out, less time-consuming, safer and economical alternative for preliminary in vivo screening of potential anti-tubercular agents.

Component wear after total knee arthroplasty (TKA) with extruded metallosis in the extra-articular tissue of the calf secondary to a periprosthetic fracture is a rare complication. A 77-year-old man with a failed Insall-Burstein II TKA prosthesis presented with calf cellulitis after a fall. Radiologic evaluation revealed severe osteolysis and loosening of prosthetic components and an intramuscular abscess communicating with the medullary canal of the tibia through an undisplaced periprosthetic fracture. The patient developed rhabdomyolysis with acute renal failure. Drainage of the calf abscess showed staining of the muscles with wear debris and metallosis. The patient subsequently had debridement and excision of the infected TKA implant. Prompt diagnosis of this condition should be suspected in cases of failed arthroplasty with osteolysis and periprosthetic fracture.

Background: Presently, in vitro and in vivo screening of anti-tubercular drugs is a time-consuming exercise. Therefore, it is important to develop faster methods., Material and Methods: Towards this end, conventional plating and radiometric BACTEC methods of anti-tubercular screening were compared to determine the efficacy of anti-tubercular drugs (isoniazid and rifampicin) and morphine in Mycobacterium tuberculosis H37Rv-infected mice and macrophages., Results: A linear correlation (R2 = 0.95) was observed between number of colony forming units (CFUs) and growth index (GI) values. BACTEC method was found to be faster and sensitive as compared to plating method. Further, BACTEC method, being a closed system, appeared to be less susceptible to microbial contamination and poses less biohazard., Conclusion: We conclude that BACTEC method can be employed for easy, precise, and rapid screening of anti-tubercular compounds and morphine in mice and macrophage models.

The effects of opiates in various infections are well known; however, very little is known about tuberculosis infection. Therefore, in the present study, we report for the first time, the effects of morphine during murine tuberculosis. Mice were infected intravenously with Mycobacterium tuberculosis H37Rv, administered morphine (0.1-100 mg/kg subcutaneously on day 0 and day +15) and sacrificed on day +30 for CFU enumeration in lungs and spleen. Morphine exerted maximum suppression of infection at 5 mg/kg, and sometimes completes elimination of infection; naloxone, silica and aminoguanidine blocked the protective effect of morphine. In vitro, morphine lacked direct antimycobacterial activity up to 1x10(-4) M concentration, as assessed by radiometric BACTEC method. In macrophage model of infection, morphine showed maximal killing at 1x10(-7) M concentration, the activity was blocked by naloxone and aminoguanidine. These observations suggest that morphine exerts a dose-dependent effect in murine tuberculosis, the protective effect being naloxone-reversible and may involve macrophage-mediated protective mechanisms. These results may be helpful in developing new opioid-like chemical entities against tuberculosis infection.

Additional structural modifications of the new chemical entity, 2,8-dicyclopentyl-4-methylquinoline (DCMQ; MIC=6.25 microg/mL, M. tuberculosis H37Rv) resulted in the synthesis of four new series of the ring-substituted quinolinecarbohydrazides (series 1-4) constituting 22 analogues. All new derivatives were evaluated for in vitro antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv strain. Certain ring-substituted-2-quinolinecarbohydrazide analogues described herein showed good inhibitory activity. In particular, analogues 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d), 4,5-dicyclopentyl-2-quinolinecarbohydrazide (2e), 4,8-dicyclopentyl-2-quinolinecarbohydrazide (2f), and 4,5-dicyclohexyl-2-quinolinecarbohydrazide (2g) have exhibited the MIC value of 6.25 microg/mL. Further investigation of the most suitable lead prototype, 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d, series 1) led to the synthesis of N2-alkyl/N2,N2-dialkyl/N2-aryl-4-(1-adamantyl)-2-quinolinecarboxamides (series 5) consisting of 13 analogues. Some of the synthesized carboxamides 7a, 7h, and 7m reported herein have exhibited excellent antimycobacterial activities in the range of 6.25-3.125 microg/mL against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains.