Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study.

OBJECTIVE: Argininosuccinate lyase (ASL) is integral to the urea cycle, which enables nitrogen wasting and biosynthesis of arginine, a precursor of nitric oxide. Inherited ASL deficiency causes argininosuccinic aciduria, the second most common urea cycle defect and an inherited model of systemic nitric oxide deficiency. Patients present with developmental delay, epilepsy, and movement disorder. Here we aim to characterize epilepsy, a common and neurodebilitating comorbidity in argininosuccinic aciduria. METHODS: We conducted a retrospective study in seven tertiary metabolic centers in the UK, Italy, and Canada from 2020 to 2022, to assess the phenotype of epilepsy in argininosuccinic aciduria and correlate it with clinical, biochemical, radiological, and electroencephalographic data. RESULTS: Thirty-seven patients, 1-31 years of age, were included. Twenty-two patients (60%) presented with epilepsy. The median age at epilepsy onset was 24 months. Generalized tonic-clonic and focal seizures were most common in early-onset patients, whereas atypical absences were predominant in late-onset patients. Seventeen patients (77%) required antiseizure medications and six (27%) had pharmacoresistant epilepsy. Patients with epilepsy presented with a severe neurodebilitating disease with higher rates of speech delay (p = .04) and autism spectrum disorders (p = .01) and more frequent arginine supplementation (p = .01) compared to patients without epilepsy. Neonatal seizures were not associated with a higher risk of developing epilepsy. Biomarkers of ureagenesis did not differ between epileptic and non-epileptic patients. Epilepsy onset in early infancy (p = .05) and electroencephalographic background asymmetry (p = .0007) were significant predictors of partially controlled or refractory epilepsy. SIGNIFICANCE: Epilepsy in argininosuccinic aciduria is frequent, polymorphic, and associated with more frequent neurodevelopmental comorbidities. We identified prognostic factors for pharmacoresistance in epilepsy. This study does not support defective ureagenesis as prominent in the pathophysiology of epilepsy but suggests a role of central dopamine deficiency. A role of arginine in epileptogenesis was not supported and warrants further studies to assess the potential arginine neurotoxicity in argininosuccinic aciduria.

A New RP-HPLC Method for Simultaneous Determination of Amaroswerin, Amarogentin and Andrographolide in a Herbal Drug "Chirayata".

Chirayata-the whole dried plant of Swertia chirayita-is an important traditional drug of Indian System of Medicines. A novel reverse-phase high performance liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination and quantification of amaroswerin, amarogentin and andrographolide in a herbal drug "Chirayata," which is oftenly adulterated/substituted with herbal drug Kalmegh. The developed method is in accordance with International Council for Harmonization guidelines and is simple, precise, accurate, rapid, reproducible and specific to determine amarogentin, amaroswerin and andrographolide. Reverse-phase column (Water's X-bridge C18, 5 µm, 4.6 mm × 250 mm) with high resolution for all marker compounds was used with binary gradient elution (methanol:water) with a flow rate of 1 mL/min and detection at 235 nm. The developed method showed good linearity (R2 > 0.999) in a relatively wider range of concentration 2.968-95.00 ppm for amarogentin, amaroswerin and 5.625-180 ppm for andrographolide. The method is important for quality control analysis of drug Chirayata.

The clinico-epidemiological characteristics and therapeutic experience of 152 patients with cutaneous sporotrichosis: a 10-year retrospective study from India.

BACKGROUND: Cutaneous sporotrichosis, a subcutaneous mycosis because of Sporothrix schenckii, is sporadic worldwide with local hyperendemic pockets. OBJECTIVES: To study clinico-epidemiological and therapeutic aspects of sporotrichosis in our clinic. METHODS: We retrospectively analyzed medical records of 152 (M:F 52:100) patients with cutaneous sporotrichosis managed during 2010-2019. RESULTS: All patients were involved in agricultural activities, and 63.2% were aged 21-60 years. Women outnumbered men by nearly two times. Fixed and lymphocutaneous sporotrichosis occurred in 54.6% and 43.4% patients, respectively. Only 2% of patients had multifocal sporotrichosis. Only 48% of patients imputed their disease to prior injuries. Extremities, upper in 53.9% and lower in 21% of patients, were mostly involved. Scrotum involvement in one patient was unusual. A mixed inflammatory infiltrate in 38.7%, chronic granuloma formation in 35%, and presence of spores in 48.9% biopsies was noted. S. schenckii grew on Sabouraud's dextrose agar in 40.2% of cases. Treatment with saturated solution of potassium iodide was curative in 76.8% patients, and lesions healed in 2-9 months (average 5.2 months). Metallic taste was experienced by 42.9% of patients. Itraconazole therapy was safe and effective in seven patients, and the response was better when combined with SSKI compared to either drug used alone. CONCLUSION: Cutaneous sporotrichosis mostly affects persons during active years of life. The injuries predisposing to infection are mostly forgotten. Both fixed and lymphocutaneous sporotrichosis involving extremities remain common forms. SSKI alone or in combination with itraconazole is safe and effective treatment. Itraconazole is preferable in patients having preexisting hypothyroidism or intolerance to SSKI.

Chemo-Geographic Variations in Wild Population of Asteriscus graveolens in Israel Based on Volatile Composition Analyses.

Asteriscus graveolens is an aromatic desert shrub which holds medicinal potential. This species belongs to the Asteraceae family and is endemic to the Mediterranean region. In the present study, wild plants were sampled from eleven locations throughout southern Israel and the volatile profiles from leaves and flowers were analyzed using GC/MS. Three methods for volatile sampling were tested for a representative population: solvent extraction (methyl tert-butyl ether), hydrodistillation of the essential oil and headspace solid-phase microextraction. In all methods, the majority of volatiles were characterized as oxygenated mono- and sesquiterpenes. Only solvent extraction was able to detect asteriscunolides that were previously reported as anticancer molecules. Hence, that method was chosen for further analyses. The leaves were dominated by three asteriscunolide isomers, cis-chrysanthenyl acetate and intermedeol. The flowers were dominated by bisabolone, 6-hydroxybisabol-2-en-1-one, cis-chrysanthenyl acetate, epi-α-cadinol, and germacrene-D. k-Means clustering analysis of these data divided the population into four clusters that significantly differ in their volatile composition as was further demonstrated by MANOVA analysis. Geographically, A. graveolens populations growing in Israel were found to be chemically diverse with unique varieties in the Dead Sea basin and the Arava region. This work demonstrates that chemo-geographic variation of volatile composition exists within A. graveolens population growing in Israel, so future research evaluating the medicinal potential of that plant should take this into consideration.

Knowledge and practice of, and attitudes toward, pulp therapy in deciduous teeth among pediatric dentists in India.

AIM: The aim of the present study was to assess the knowledge and practice of, and attitudes toward, pulp therapy in deciduous dentition among pediatric dentists. METHODS: A cross-sectional, observational survey was conducted using a closed-ended, multiple-choice questionnaire evaluating the knowledge and practice of, and attitudes toward, pulp therapy in deciduous dentition, which was formulated and sent to 360 pediatric dentists across India. Descriptive statistics were done, followed by χ2 -test to test the association between years of experience and the questionnaire items. RESULTS: A total of 3.5% of pediatric dentists performed their treatment using a rubber dam in all cases; 30% preferred to use local anesthesia prior to indirect pulp therapy (IPT). Traditional indirect pulp capping was preferred to IPT, and only 48% of them believed in not removing it completely. Pulpotomy was preferred over IPT (70%) when there was a probability of pulp exposure following complete caries excavation. Calcium hydroxide, along with iodoform, was the material of choice for the obturation of primary teeth (73.5%). A stainless steel crown was placed after pulp therapy in the primary tooth (86.3%). Most dentists believed requested immediate and 3-month follow up. CONCLUSION: The survey helps in assessing whether our views or approaches are in line with recent trends.