Anti-diabetic and anti-inflammatory bioactive hits from Coriaria intermedia Matsum. stem and Dracontomelon dao (Blanco) Merr. & Rolfe bark through bioassay-guided fractionation and liquid chromatography-tandem mass spectrometry.

Women have been found to be at a higher risk of morbidity and mortality from type 2 diabetes mellitus (T2DM) and asthma. α-Glucosidase inhibitors have been used to treat T2DM, and arachidonic acid 15-lipoxygenase (ALOX15) inhibitors have been suggested to be used as treatments for asthma and T2DM. Compounds that inhibit both enzymes may be studied as potential treatments for people with both T2DM and asthma. This study aimed to determine potential anti-diabetic and anti-inflammatory bioactive hits from Coriaria intermedia Matsum. stem and Dracontomelon dao (Blanco) Merr. & Rolfe bark. A bioassay-guided fractionation framework was used to generate bioactive fractions from C. intermedia stem and D. dao bark. Subsequently, dereplication through ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and database searching was performed to putatively identify the components of one bioactive fraction from each plant. Seven compounds were putatively identified from the C. intermedia stem active fraction, and six of these compounds were putatively identified from this plant for the first time. Nine compounds were putatively identified from the D. dao bark active fraction, and seven of these compounds were putatively identified from this plant for the first time. One putative compound from the C. intermedia stem active fraction (corilagin) has been previously reported to have inhibitory activity against both α-glucosidase and 15-lipoxygenase-1. It is suggested that further studies on the potential of corilagin as an anti-diabetic and anti-inflammatory treatment should be pursued based on its several beneficial pharmacological activities and its low reported toxicity.

Psychiatry Resident Education in Neurocognitive Disorders: a National Survey of Program Directors in Psychiatry.

OBJECTIVE: As major neurocognitive disorders increase, little research has examined how psychiatry residents are prepared to provide neurocognitive care to patients. METHODS: A national survey was sent to program directors of general psychiatry in the USA and Canada, including questions about satisfaction, attitudes, and graduation expectations for training in major neurocognitive disorders. The authors examined descriptive statistics and a series of chi-squared analyses by training setting, residency type, and presence of subspecialty fellowships. The authors also collected free text responses about perceived needs for enhancing training. RESULTS: Program directors agreed that the scope of general psychiatry includes the evaluation of cognitive disorders (78.8%) and the treatment of cognitive symptoms (77.5%) and behavioral/psychological symptoms (78.8%). Required clinical rotations were the preferred method of teaching (63.7%), but didactics were most used (93.8%). The most frequently used clinical teaching setting was geriatric psychiatry (61.3%) and didactics were most frequently taught by geriatric psychiatrists (75.0%). Fifty-six percent were satisfied or very satisfied with their clinical training and 66.3% with their didactics. There were no significant differences in satisfaction or attitudes when compared by training setting, residency type, or presence of subspecialty fellowships. Additional trained faculty were most frequently listed as a need for improving clinical and didactic training. CONCLUSIONS: Psychiatry program directors view major neurocognitive disorders as part of the scope of psychiatric practice. The majority of training is provided within psychiatry rotations, especially geriatric psychiatry. Program directors reported several unmet needs for optimal training, particularly related to clinical training services.

Current Educational Practices for Major Neurocognitive Disorders in Psychiatry: a Scoping Review.

OBJECTIVE: A scoping review of the literature was performed to examine the current state of education on major neurocognitive disorders within psychiatry, to review influential factors for pursuing a career working with these patients, and to review what has been done in education to address the shortage of providers to care for patients with major neurocognitive disorders. METHODS: Using the Arksey and O'Malley framework for conducting scoping reviews, twenty-eight studies on education in geriatric psychiatry, neuropsychiatry, and major neurocognitive disorders were selected. Learner groups included medical students, residents, and psychiatrists. The results from the studies were compared, and major themes were presented. RESULTS: Several studies found that positive clinical experiences with older adult patients and effective teachers in geriatric psychiatry play a role in influencing trainees to pursue a career in geriatric psychiatry. Topics pertaining to major neurocognitive disorders are taught by the majority of medical schools during the psychiatry rotation and are rated as the most important teaching topic in neurology among psychiatry residency program directors. Several interventions have resulted in increased comfort working with geriatric patients and patients who have major neurocognitive disorders among students, but fewer studies have resulted in an increase in interest seeing these patients in practice. There is a lack of research pertaining to psychiatry residents working with patients that have major neurocognitive disorders. CONCLUSIONS: While research on geriatric psychiatry and neuropsychiatry education exists, more research is needed that focuses specifically on how medical students and psychiatry residents are being taught major neurocognitive disorders.

Rats concatenate 22 kHz and 50 kHz calls into a single utterance.

Traditionally, the ultrasonic vocal repertoire of rats is differentiated into 22 kHz and 50 kHz calls, two categories that contain multiple different call types. Although both categories have different functions, they are sometimes produced in the same behavioral context. Here, we investigated the peripheral mechanisms that generate sequences of calls from both categories. Male rats, either sexually experienced or naïve, were exposed to an estrous female. The majority of sexually naïve male rats produced 22 kHz and 50 kHz calls on their first encounter with a female. We recorded subglottal pressure and electromyographic activity of laryngeal muscles and found that male rats sometimes concatenate long 22 kHz calls and 50 kHz trill calls into an utterance produced during a single breath. The qualitatively different laryngeal motor patterns for both call types were produced serially during the same breathing cycle. The finding demonstrates flexibility in the laryngeal-respiratory coordination during ultrasonic vocal production, which has not been previously documented physiologically in non-human mammals. Since only naïve males produced the 22 kHz-trills, it is possible that the production is experience dependent.

Pluripotent cells display enhanced resistance to mutagenesis.

Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate. We also measured levels of key enzymes in the base excision repair (BER) pathway in each cell line before and after exposure to the mutagen. Our results confirm that pluripotent cells normally maintain lower frequencies of point mutations than differentiated cells, and show that differentiated cells exhibit a large increase in mutation frequency following a moderate mutagenic exposure, whereas pluripotent cells subjected to the same exposure show no increase in mutations. This result likely reflects the higher levels of BER proteins detectable in pluripotent cells prior to exposure and supports our thesis that maintenance of enhanced genetic integrity is a fundamental characteristic of pluripotent cells.

Dynamic Variations in Genetic Integrity Accompany Changes in Cell Fate.

Pluripotent stem cells hold the potential to form the basis of novel approaches to treatment of disease in vivo as well as to facilitate the generation of models for human disease, providing powerful avenues to discovery of novel diagnostic biomarkers and/or innovative drug regimens in vitro. However, this will require extensive maintenance, expansion, and manipulation of these cells in culture, which raises a concern regarding the extent to which genetic integrity will be preserved throughout these manipulations. We used a mutation reporter (lacI) transgene approach to conduct direct comparisons of mutation frequencies in cell populations that shared a common origin and genetic identity, but were induced to undergo transitions in cell fate between pluripotent and differentiated states, or vice versa. We confirm that pluripotent cells normally maintain enhanced genetic integrity relative to that in differentiated cells, and we extend this finding to show that dynamic transformations in the relative stringency at which genetic integrity is maintained are associated with transitions between pluripotent and differentiated cellular states. These results provide insight into basic biological distinctions between pluripotent and differentiated cell types that impact genetic integrity in a manner that is directly relevant to the potential clinical use of these cell types.

The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats.

Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever-pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine's effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine's appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking.

New steroidal saponin from Antigonon leptopus Hook. and Arn.

BACKGROUND: Antigonon leptopus Hook. and Arn., Polygonaceae (cadena de amor), is a herbal remedy for pain and gout-like symptoms in the Philippines. The methanol extract of A. leptopus have shown strong inhibitory action against xanthine oxidase. OBJECTIVE: To isolate and identify the compound responsible for the xanthine oxidase inhibitory action. MATERIALS AND METHODS: A bioassay-guided isolation scheme using an in vitro assay for the inhibition of xanthine oxidase was employed. The structure was established using spectroscopic analysis and chemical methods. RESULTS: The isolated compound was determined to be a noncompetitive inhibitor of xanthine with an IC50 of 1.79 µg/mL. CONCLUSION: The isolated compound may represent a new class of xanthine oxidase inhibitors.

15-Lipoxygenase inhibition of Commelina benghalensis, Tradescantia fluminensis, Tradescantia zebrina.

OBJECTIVE: To evaluate the 15-lipoxygenase inhibitory activity of the methanol leaf extracts of Commelina benghalensis, Tradescantia fluminensis (T. fluminensis) and Tradescantia zebrina. METHOD: The inhibitory activity was evaluated using a spectrophotometric assay by observing the increase in absorbance at 234 nm due to the formation of the product 13-hydroperoxyoctadecadienoic acid. The extracts were also tested for the presence of terpenoids, saponins, tannins, flavonoids, steroids, phenolic compounds, alkaloids and cardiac glycosides. RESULTS: All the extracts inhibited the action of 15-lipoxygenase at a concentration of 0.2 µg/mL. T. fluminensis and Tradescantia zebrina exhibited higher than 50% inhibition with T. fluminensis at 87.2%. T. fluminensis was partitioned with ethyl acetate and hexane and their IC50 values were determined at 8.72 µg/mL and 98.04 µg/mL, respectively. CONCLUSIONS: T. fluminensis is a potentially good source of 15-lipoxygenase inhibitors.

Anti-ulcer activity of leguminosae plants.

CONTEXT: Ulcer is the most common gastrointestinal disturbance resulting from an inadequate gastric mucosal defense. Several drugs are available in the market to address the disease; however, these drugs are associated with unnecessary side effects. OBJECTIVES: Previous research have confirmed the efficacy of plant extracts for possible treatment of the disease. This research aims to evaluate the anti-ulcer properties of medicinal plants. METHODS: Methanol extracts from the leaves of Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea and Saraca thaipingensis were evaluated for their anti-ulcer activity using HCl-ethanol as ulcerogen. RESULTS: All extracts showed inhibitory activity with I. bijuga, T. indica, S. spectabilis and S. thaipingensis exhibiting more than 50% inhibition. S. thaipingensis showed the highest activity at 80%. S. spectabilis and S. thaipingensis were partitioned further into hexane, ethyl acetate and aqueous fractions. The aqueous and ethyl acetate fractions of S. spectabilis showed significant increased in its activity while the hexane and ethyl acetate fractions of S. thaipingensis gave higher activity than its aqueous portions. CONCLUSIONS: We conclude that plant extracts are potential sources of new anti-ulcer agents.

Anti-ulcer actviity of leguminosae plants / Atividade anti-úlcera de plantas leguminosas

Context Ulcer is the most common gastrointestinal disturbance resulting from an inadequate gastric mucosal defense. Several drugs are available in the market to address the disease; however, these drugs are associated with unnecessary side effects. Objectives Previous research have confirmed the efficacy of plant extracts for possible treatment of the disease. This research aims to evaluate the anti-ulcer properties of medicinal plants. Methods Methanol extracts from the leaves of Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea and Saraca thaipingensis were evaluated for their anti-ulcer activity using HCl-ethanol as ulcerogen. Results All extracts showed inhibitory activity with I. bijuga, T. indica, S. spectabilis and S. thaipingensis exhibiting more than 50% inhibition. S. thaipingensis showed the highest activity at 80%. S. spectabilis and S. thaipingensis were partitioned further into hexane, ethyl acetate and aqueous fractions. The aqueous and ethyl acetate fractions of S. spectabilis showed significant increased in its activity while the hexane and ethyl acetate fractions of S. thaipingensis gave higher activity than its aqueous portions. Conclusions We conclude that plant extracts are potential sources of new anti-ulcer agents. .

Contexto A úlcera é o distúrbio gastrointestinal mais comum que resulta de uma inadequada defesa da mucosa gástrica. Vários medicamentos estão disponíveis no mercado para tratar a doença, no entanto, estas drogas podem se associar a efeitos colaterais desnecessários. Objetivos Pesquisas anteriores confirmaram a eficácia de extratos de plantas como possível tratamento da doença. Esta pesquisa teve como objetivo avaliar as propriedades anti-úlcera de plantas medicinais. Métodos Extratos alcoólicos das folhas da Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea e Saraca thaipingensis foram avaliados pela sua atividade anti-úlcera usando o HCl-etanol como ulcerogênico. Resultados Todos os extratos apresentaram atividade inibitória; I.bijuga, T. Índica, S. spectabilis e S. thaipingensis mostraram mais de 50% de inibição. A S. thaipingensis mostrou a maior atividade, atingindo 80%. S. spectabilis e S. thaipingensis foram divididos mais em hexano, acetato de etila e frações aquosas. As frações aquosas e acetato de etila de S. spectabilis mostraram aumento significativo em sua atividade, enquanto que as frações hexano e acetato de etila de S. thaipingensis resultaram em maior atividade do que em partes aquosas. Conclusões Pode-se concluir que os extratos vegetais são fontes potenciais de novos agentes anti-úlcera. .

Evaluation of cytotoxicity and genotoxicity of some Philippine medicinal plants.

The genotoxicity and toxicity of ethnomedicinal Philippine plants, which include Cassia fistula, Derris elliptica, Ficus elastica, Gliciridia sepium, Michelia alba, Morus alba, Pogostemon cablin and Ricinus communis, were tested using the Vitotox assay. The plants are used traditionally to treat several disorders like diabetes, weakness, menorrhagia, headache, toothache and rheumatism. The dried leaves were homogenized for overnight soaking in methanol at room temperature. The resulting alcoholic extracts were filtered and concentrated in vacuo and tested for their genotoxicity and cytotoxicity using Vitotox®. Results showed that the medicinal plants that were tested are not genotoxic nor cytotoxic, except for R. communis and P. cablin, which showed toxicity at high doses (low dilutions) in the absence of S9.