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Background: Calcium channel blockers, including the recently developed cilnidipine, are widely used as first-line medications for treating newly diagnosed cases of primary essential hypertension. Cilnidipine has a unique advantage compared to amlodipine, another common calcium channel blocker. While amlodipine only targets L-type calcium channels, cilnidipine can target both L and N-type channels. This study aimed to compare the effectiveness and safety of these two medications in patients with essential hypertension. Methods: A total of n=80 cases of mild to moderate hypertension were randomly allocated to two groups. Group I n=40 received a daily dose of Amlodipine 5mg, whereas those in Group II n=40 received Cilnidipine 10mg once daily, 30 minutes after breakfast, for 8 weeks. Participants were prohibited from using any other medications during the study period. Each patient underwent three visits: a baseline visit (Visit 0) on recruitment day, visit 1 after 30 days of medication, and Visit 2 after 60 days of treatment. Systolic and diastolic blood pressures, as well as heart rate, were measured at each visit. Clinical and laboratory parameters were reassessed at the end of the 8 weeks. Results: Both medications significantly reduced Systolic and Diastolic Blood Pressure (SBP and DBP) and heart rate in both groups over 8 weeks. While Group II (Cilnidipine) consistently showed slightly lower blood pressure and heart rate, these differences were statistically insignificant, suggesting similar effectiveness between the two medications in this study. Both groups reported mild/moderate adverse events, with Group I having a consistently higher number and wider range of events compared to Group II. The most common events were fatigue and headache, with Group I experiencing additional events like headache + GI upset, vomiting, and ankle edema. Conclusion: Both the calcium channel blockers amlodipine and cilnidipine exhibit equivalent efficacy in reducing systolic and diastolic blood pressure in patients with mild to moderate essential hypertension. Cilnidipine, as a fourth-generation calcium channel blocker, offers a promising pharmacological profile. In addition to its blood pressure-lowering effects, cilnidipine demonstrates notable safety and provides additional benefits including renoprotective, cardioprotective, and neuroprotective effects. [ABSTRACT FROM AUTHOR]

Medical nutrition therapy interventions among type 2 diabetes patients administered by registered dieticians are said to be beneficial to the extent of reducing glycated hemoglobin by 1%–2%. Despite patient-centered dietary interventions, adherence continues to remain a challenge in the Indian setting due to the carbohydrate-rich dietary pattern, dietary myths coupled with lack of nutritional awareness, poor literacy, financial burden, and lack of motivation. On the contrary, the evolution of “FAD” diets through drastic dietary changes present individuals with type 2 diabetes with a possibility of reversal of the disease further increasing the nutritional dilemma. These FAD diets extend beyond being mere trends and show improvements in several biochemical processes by reducing the intake of calories either through restriction (very low-calorie diet) or fasting (intermittent fasting) or low carbohydrate diets up to one year. This article by evaluating the suitability of these promising diets to Indian adults with type 2 diabetes aimed to provide evidence that could improve diabetes-related dietary knowledge. Through this narrative review, we conclude that a single drastic dietary modification as seen in very low-calorie diets (≤ 800 kcal/day) or the low-carbohydrate diet (≤ 75 g/d) is not suitable for Indians and such dietary measures will further hamper the sustainability of prescribed diets. The future directions in diet and disease would be to develop clinical trials that will show the effectiveness of dietary regimens constituting optimal energy deficit and macronutrient balances that will contribute to the remission of disease while preventing macronutrient deficiencies and relapse in the dietary regimen.

Introduction: The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults., Methods: Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0., Results: Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04])., Conclusion: Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population., (© 2024. Indian Society of Gastroenterology.)

Acute myelitis encompasses syndromes associated with inflammation of the spinal cord. In cases of inflammatory lesions that only involve a unilateral portion of the axial plane of the cord, Brown-Séquard syndrome may occur, resulting in potential ipsilateral corticospinal, dorsal spinocerebellar, or dorsal column dysfunction or contralateral spinothalamic dysfunction below the level of the lesion. We report a case of an adult male who presented with Brown-Séquard syndrome and with a positive SARS-CoV-2 nasopharyngeal swab PCR test. Neurological symptoms rapidly resolved after initiation of high-dose methylprednisolone. The findings reported not only contribute to documenting a new presentation of neurological complications associated with SARS-CoV-2 infection but also non-exclusively supports the body of literature suggesting the immune-mediated response to this infection as a mechanism of neuropathogenesis. In this case, COVID-19-related acute myelitis responded to treatment with a short regimen of high-dose glucocorticoids., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We describe a patient with concurrent ocular and pulmonary tuberculosis (TB) in whom the diagnosis of extensively drug-resistant TB was made through phenotypic drug-sensitivity testing of an ocular fluid sample after sputum testing yielded incomplete results. Our results are remarkable, because culture-based diagnosis of TB in ocular fluid is unusual. We not only overcame this limitation, but also were able to create a complete drug-sensitivity testing profile from ocular samples, which led to effecting appropriate therapy for the patient.

Introduction: Lower respiratory tract infections (LRTIs) among renal transplant recipients (RTRs) are a significant cause of morbidity and mortality. This study aimed to analyse the aetiology, outcome, and risk factors associated with mortality., Methods: We analysed baseline transplant characteristics, symptoms, hospital course, laboratory, serological and microbial results, and their association with the outcome of all RTRs between January 2011 and December 2019., Results: A total of 206 LRTI patients out of 1051 RTRs were analysed. The incidence proportion was nearly 22 episodes per 1000 patients per year. The mean age was 39.3 years, with male predominance. Bacterial was the most common aetiology (53%), and staphylococcus was the most common species. Among the fungal causes (14%), 68% had aspergillus infection. More than one-third RTRs died during the hospital course mainly because of bacterial causes (42.6%). The aspergillus infection was the most common fungus associated with 50% mortality. On multi-variate analysis, sepsis, septic shock, and the need for mechanical ventilation independently predicted mortality., Conclusion: Bacterial aetiology was the most common cause; though the fungal aetiology was seen less, it was associated with higher mortality. Mortality in RTR with LRTI was associated with sepsis, septic shock, and the need for mechanical ventilation., Competing Interests: None

In this research, we study a new metaheuristic algorithm called Moth-Flame Optimization (MFO) for hyperspectral band selection. With the hundreds of highly correlated narrow spectral bands, the number of training samples required to train a statistical classifier is high. Thus, the problem is to select a subset of bands without compromising the classification accuracy. One of the ways to solve this problem is to model an objective function that measures class separability and utilize it to arrive at a subset of bands. In this research, we studied MFO to select optimal spectral bands for classification. MFO is inspired by the behavior of moths with respect to flames, which is the navigation method of moths in nature called transverse orientation. In MFO, a moth navigates the search space through a process called transverse orientation by keeping a constant angle with the Moon, which is a compelling strategy for traveling long distances in a straight line, considering that the Moon's distance from the moth is considerably long. Our research tested MFO on three benchmark hyperspectral datasets-Indian Pines, University of Pavia, and Salinas. MFO produced an Overall Accuracy (OA) of 88.98%, 94.85%, and 97.17%, respectively, on the three datasets. Our experimental results indicate that MFO produces better OA and Kappa when compared to state-of-the-art band selection algorithms such as particle swarm optimization, grey wolf, cuckoo search, and genetic algorithms. The analysis results prove that the proposed approach effectively addresses the spectral band selection problem and provides a high classification accuracy.

Introduction: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment., Materials and Method: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application., Results: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease., Conclusion: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens., Competing Interests: The authors have declared that no competing interests exist.

Objectives: N,N-Diethyl-3-methylbenzamide (DEET) is a broad-spectrum insect repellent that can easily permeate through the skin and can cause undesirable effects, especially in children and pregnant women. The objective of this research was to formulate and evaluate DEET-encapsulated microparticles containing a hydrogel designed to reduce skin permeation and prolong drug release., Materials and Methods: The formulation design was based on the independent formulation variables of the concentration of chitosan and sodium tripolyphosphate using a simple factorial design experiment. DEET-loaded microparticles were developed and incorporated into a hydrogel. The size of the microparticles was analyzed using the Zetasizer Nano ® particle size analyzer, and the surface morphology, using field emission scanning electron microscopy. Drug release from the microparticles was determined by the dialysis bag method. A rheological evaluation of the formulated gel was performed using a Thermo Haake Rheometer. The in vitro permeation of the formulation was performed using a synthetic Strat-M ® membrane., Results: The size of the microparticles ranged from 0.45 to 8.3 μm, and the encapsulation efficiencies were >50% for all the formulations. The drug-release curves showed no initial burst release from the microparticle formulation. Instead, a slow and controlled drug release was observed over 24 hours that followed Higuchi kinetics. The cumulative amount of DEET permeated (over 24 h) from the DEET solution (control), and the formulation was 211.6±19.5 μg/cm 2 and 4.07±0.08 μg/cm 2 , respectively., Conclusion: A significantly low DEET permeation from the microparticle formulations indicated minimal absorption of the drug into the body and thus, reduced systemic toxicity. Thixotropic evaluation of the hydrogel formulation demonstrated a hysteresis loop that fitted closely to the Herschel-Bulkley rheological model, ensuring an effortless application and prolonged retention on the skin. Hence, it can be concluded that the developed formulation is an effective delivery approach for controlled insect repellent activity with reduced skin absorption.

Metal halide lights (MHLs) emit ultraviolet radiation (UVR) and should be used with enclosed fixtures. We investigated a cluster of blurred vision in a locality in South India reported among light music event attendees to identify risk factors., Methods: We searched for attendees with any eye-related symptoms by door-to-door. We described cases by time, place, and person and inspected the environment to generate a hypothesis. We followed-up the cohort of the attendees to examine the hypothesis of exposure to MHL as the cause of the outbreak. We computed relative risk (RR) and 95% confidence interval (CI) by comparing attack rates among attendees by seating location and duration of exposure., Results: Of the total 500 attendees, we could interview 319 (64%) and 89% (284/319) attendees developed bilateral photokeratitis (median age = 24 years [range: 2-80 years]). Attack rate was higher among female (92% [172/189]) than male (85% [110/130]). Attack rate among those seated within 12 meters from dais was higher (95% [241/253]) than the rest (65% [43/66]; RR = 1.5; 95% CI = 1.2, 1.7) and attack rate was higher among those continuously exposed to MHL (97% [268/277]) than others (38% [16/42]; RR = 2.5; 95% CI = 1.7, 3.7). The duration of exposure was associated with increased risk of bilateral photokeratitis (χ 2 test for linear trend = 74; P < 0.00001). During the environmental inspection, we identified the use of MHL with a broken outer envelope., Conclusions: Photokeratitis was associated with exposure to UVR from MHL with a broken outer envelope. We recommended the usage of MHL along with enclosed fixtures., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.)

Objective: To evaluate the efficacy of a portable, wearable, wireless artificial pancreas system (the Diabetes Assistant [DiAs] running the Unified Safety System) on glucose control at home in overnight-only and 24/7 closed-loop control (CLC) modes in patients with type 1 diabetes., Research Design and Methods: At six clinical centers in four countries, 30 participants 18-66 years old with type 1 diabetes (43% female, 96% non-Hispanic white, median type 1 diabetes duration 19 years, median A1C 7.3%) completed the study. The protocol included a 2-week baseline sensor-augmented pump (SAP) period followed by 2 weeks of overnight-only CLC and 2 weeks of 24/7 CLC at home. Glucose control during CLC was compared with the baseline SAP., Results: Glycemic control parameters for overnight-only CLC were improved during the nighttime period compared with baseline for hypoglycemia (time <70 mg/dL, primary end point median 1.1% vs. 3.0%; P < 0.001), time in target (70-180 mg/dL: 75% vs. 61%; P < 0.001), and glucose variability (coefficient of variation: 30% vs. 36%; P < 0.001). Similar improvements for day/night combined were observed with 24/7 CLC compared with baseline: 1.7% vs. 4.1%, P < 0.001; 73% vs. 65%, P < 0.001; and 34% vs. 38%, P < 0.001, respectively., Conclusions: CLC running on a smartphone (DiAs) in the home environment was safe and effective. Overnight-only CLC reduced hypoglycemia and increased time in range overnight and increased time in range during the day; 24/7 CLC reduced hypoglycemia and increased time in range both overnight and during the day. Compared with overnight-only CLC, 24/7 CLC provided additional hypoglycemia protection during the day., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To evaluate the feasibility and efficacy of a fully integrated hybrid closed-loop (HCL) system (Medtronic MiniMed Inc., Northridge, CA), in day and night closed-loop control in subjects with type 1 diabetes, both in an inpatient setting and during 6 days at diabetes camp., Research Design and Methods: The Medtronic MiniMed HCL system consists of a fourth generation (4S) glucose sensor, a sensor transmitter, and an insulin pump using a modified proportional-integral-derivative (PID) insulin feedback algorithm with safety constraints. Eight subjects were studied over 48 h in an inpatient setting. This was followed by a study of 21 subjects for 6 days at diabetes camp, randomized to either the closed-loop control group using the HCL system or to the group using the Medtronic MiniMed 530G with threshold suspend (control group)., Results: The overall mean sensor glucose percent time in range 70-180 mg/dL was similar between the groups (73.1% vs. 69.9%, control vs. HCL, respectively) (P = 0.580). Meter glucose values between 70 and 180 mg/dL were also similar between the groups (73.6% vs. 63.2%, control vs. HCL, respectively) (P = 0.086). The mean absolute relative difference of the 4S sensor was 10.8 ± 10.2%, when compared with plasma glucose values in the inpatient setting, and 12.6 ± 11.0% compared with capillary Bayer CONTOUR NEXT LINK glucose meter values during 6 days at camp., Conclusions: In the first clinical study of this fully integrated system using an investigational PID algorithm, the system did not demonstrate improved glucose control compared with sensor-augmented pump therapy alone. The system demonstrated good connectivity and improved sensor performance., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The present work focused on identification of allelochemicals from the leaf leachates of Gmelina arborea and analyzing its influence on the germination of red gram, green gram, black gram, and chickpea in terms of the levels of some important germination enzymes like acid phosphatase, catalase, peroxidase, and amylase. The study showed that allelopathic effects were more predominant in chickpea with 80% followed by red gram, green gram, and black gram where the inhibition ranged between 26% and 75%. The vigor index in the seed lots is also considerably reduced. Total chlorophyll content was also reduced by allelopathic effect in all treated seeds ranging between 0.7 and 7.5 μg/g dry weight. The effect of allelochemicals drastically reduced the relative water content in red gram followed by the other seed lots. The total protein content varied considerably in the control and the treated seed lots. Allelochemicals inhibited the expression and activity of the enzymes required for efficient germination. The present study also threw limelight on the effective use of this tree, wherein planting this tree amidst pulse related herb plantations could affect the growth of the economically viable plants, but this tree can very well adapt to diversified soil conditions and rainfall zones.

This pilot study evaluated the difference in accuracy between the Bayer Contour® Next (CN) and HemoCue® (HC) glucose monitoring systems in children with type 1 diabetes participating in overnight closed-loop studies. Subjects aged 10-18 years old were admitted to a clinical research center and glucose values were obtained every 30 minutes overnight. Glucose values were measured using whole blood samples for CN and HC readings and results were compared to Yellow Springs Instrument (YSI) reference values obtained with plasma from the same sample. System accuracy was compared using mean absolute relative difference (MARD) and International Organization for Standardization (ISO) accuracy standards. A total of 28 subjects were enrolled in the study. Glucose measurements were evaluated at 457 time points. CN performed better than HC with an average MARD of 3.13% compared to 10.73% for HC (P < .001). With a limited sample size, CN met ISO criteria (2003 and 2013) at all glucose ranges while HC did not. CN performed very well, and would make an excellent meter for future closed-loop studies outside of a research center., (© 2014 Diabetes Technology Society.)

Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.

Background: The major neurovascular involvement and large primary tumors are indication of amputation. The present study is an attempt to explore the feasibility of a limb salvage surgery in extremity sarcoma cases with major vessel involvement. Oncological outcomes and surgery-related morbidities are compared with those reported in literature., Materials and Methods: A retrospective review of all limb salvage surgeries done in our department between 2005 and 2008 was done and four cases of extremity sarcoma of lower limb involving femoral vessels analyzed. Interpretation of data from these cases, along with review of literature, is done., Results: In all these cases a wide monobloc excision was done adhering to oncological principles. This required resection of superficial femoral artery alone in two cases, resection of superficial femoral artery along with common femoral vein and femoral nerve in another, and of common femoral vein alone in yet another. Reconstruction was done in all these cases with reversed long saphenous vein graft. Histopathology of resected margins was free of tumor in all the four patients. One patient developed local recurrence and one developed distant metastsis. Two were disease free for one year with good functional limb, one has been disease-free for three years and another was disease-free at two years, after which he defaulted further follow-up. One patient developed arterial blowout which required ligation of common femoral artery which resulted in gangrene of the limb. He underwent amputation., Conclusion: Major neurovascular involvement in extremity sarcoma is not considered a contraindication for limb salvage surgery. Review of literature also supports our view. Post-operative wound related complications are more in this group of patients. However, long term functional outcome is good. Literature suggests a good long term local control after vascular resection and reconstruction.

The heme biosynthetic pathway of the malaria parasite is a drug target and the import of host delta-aminolevulinate dehydratase (ALAD), the second enzyme of the pathway, from the red cell cytoplasm by the intra erythrocytic malaria parasite has been demonstrated earlier in this laboratory. In this study, ALAD encoded by the Plasmodium falciparum genome (PfALAD) has been cloned, the protein overexpressed in Escherichia coli, and then characterized. The mature recombinant enzyme (rPfALAD) is enzymatically active and behaves as an octamer with a subunit Mr of 46,000. The enzyme has an alkaline pH optimum of 8.0 to 9.0. rPfALAD does not require any metal ion for activity, although it is stimulated by 20-30% upon addition of Mg2+. The enzyme is inhibited by Zn2+ and succinylacetone. The presence of PfALAD in P. falciparum can be demonstrated by Western blot analysis and immunoelectron microscopy. The enzyme has been localized to the apicoplast of the malaria parasite. Homology modeling studies reveal that PfALAD is very similar to the enzyme species from Pseudomonas aeruginosa, but manifests features that are unique and different from plant ALADs as well as from those of the bacterium. It is concluded that PfALAD, while resembling plant ALADs in terms of its alkaline pH optimum and apicoplast localization, differs in its Mg2+ independence for catalytic activity or octamer stabilization. Expression levels of PfALAD in P. falciparum, based on Western blot analysis, immunoelectron microscopy, and EDTA-resistant enzyme activity assay reveals that it may account for about 10% of the total ALAD activity in the parasite, the rest being accounted for by the host enzyme imported by the parasite. It is proposed that the role of PfALAD may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite.

A facile construction of the typical framework of narcissus alkaloids has been realized by virtue of the development of a practical route involving stereocontrolled epoxide formation and SnCl(4)-catalyzed arene-epoxide coupling. To achieve this goal, it proved to be necessary to devise a strategy that would enable chemical transformations to install an epoxy moiety in a congested environment. The successful preparation of a hindered epoxide from O-isopropylidene-protected 4-aminocyclohexenol required three steps consisting principally of controlled bromohydration and base-promoted closure and N-alkylation. It was found that a catalytic amount of SnCl(4) not only maintained the catalytic cycle but also effected clean arylation to form a fused BC ring system. Several tactics that ultimately proved to be unsatisfactory are also discussed in an effort to set important boundary limits on arene-epoxide coupling. The requisite enantiopure 4-aminocyclohexenol was available via an asymmetric cycloaddition of diene to camphor-based chloronitroso. The total synthesis of (+)-narciclasine was realized in nine steps with an overall yield of 19%.