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In the face of the global pandemic of COVID 19, approaching 1.75 Million infected worldwide (4/12/2020) and associated mortality (over 108, 000 as of 4/12/2020) as well-as other catastrophic events including the opioid crisis, a focus on brain health seems prudent [1] (https://www.coronavirus.gov). This manuscript reports on the systemic benefits of restoring and achieving dopamine homeostasis to reverse and normalize thoughts and behaviors of Reward Deficiency Syndrome (RDS) dysfunctional conditions and their effects on behavioral physiology; function of reward genes; and focuses on digestive, immune, eye health, and the constellation of symptomatic behaviors. The role of nutrigenomic interventions on restoring normal brain functions and its benefits on these systems will be discussed. We demonstrate that modulation of dopamine homeostasis using nutrigenomic dopamine agonists, instead of pharmaceutical interventions, is achievable. The allied interlinking with diverse chronic diseases and disorders, roles of free radicals and incidence of anaerobic events have been extensively highlighted. In conjunction, the role of dopamine in aspects of sleep, rapid eye movement and waking are extensively discussed. The integral aspects of food indulgence, the influence of taste sensations, and gut-brain signaling are also discussed along with a special emphasis on ocular health. The detailed mechanistic insight of dopamine, immune competence and the allied aspects of autoimmune disorders are also highlighted. Finally, the integration of dopamine homeostasis utilizing a patented gene test and a research-validated nutrigenomic intervention are presented. Overall, a cutting-edge nutrigenomic intervention could prove to be a technological paradigm shift in our understanding of the extent to which achieving dopamine homeostasis will benefit overall health.
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Steroid hormone-regulated differentiation of uterine stromal cells, known as decidualization, is essential for embryo implantation. The role of the estrogen receptor-α (ESR1) during this differentiation process is unclear. Development of conditional Esr1-null mice showed that deletion of this gene in both epithelial and stromal compartments of the uterus leads to a complete blockade of decidualization, indicating a critical role of ESR1 during this process. To further elucidate the cell type-specific function of ESR1 in the uterus, we created WE(d/d) mice in which Esr1 is ablated in uterine luminal and glandular epithelia but is retained in the stroma. Uteri of WE(d/d) mice failed to undergo decidualization, indicating that epithelial ESR1 contributes to stromal differentiation via a paracrine mechanism. We noted markedly reduced production of the leukemia inhibitory factor (LIF) in WE(d/d) uteri. Supplementation with LIF restored decidualization in WE(d/d) mice. Our study indicated that LIF acts synergistically with progesterone to induce the expression of Indian hedgehog (IHH) in uterine epithelium and its receptor patched homolog 1 in the stroma. IHH then induces the expression of chicken ovalbumin upstream promoter-transcription factor II, a transcription factor that promotes stromal differentiation. To address the mechanism by which LIF induces IHH expression, we used mice lacking uterine epithelial signal transducer and activator of transcription 3, a well-known mediator of LIF signaling. Our study revealed that LIF-mediated induction of IHH occurs without the activation of epithelial signal transducer and activator of transcription 3 but uses an alternate pathway involving the activation of the ERK1/2 kinase. Collectively our results provide unique insights into the paracrine mechanisms by which ESR1 directs epithelial-stromal dialogue during pregnancy establishment.
Assuntos
Decídua/crescimento & desenvolvimento , Implantação do Embrião/fisiologia , Receptor alfa de Estrogênio/metabolismo , Fator Inibidor de Leucemia/metabolismo , Comunicação Parácrina/fisiologia , Animais , Fator II de Transcrição COUP/biossíntese , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Decídua/citologia , Decídua/metabolismo , Ativação Enzimática/genética , Receptor alfa de Estrogênio/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteínas Hedgehog/biossíntese , Fator Inibidor de Leucemia/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucosa/citologia , Mucosa/metabolismo , Receptores Patched , Receptor Patched-1 , Gravidez , Progesterona/metabolismo , Receptores de Superfície Celular/biossíntese , Fator de Transcrição STAT3/genética , Transdução de Sinais/genéticaRESUMO
The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.
Assuntos
Artrite/veterinária , Condroitina/farmacologia , Colágeno Tipo II/farmacologia , Doenças do Cão/tratamento farmacológico , Glucosamina/farmacologia , Dor/veterinária , Animais , Artrite/tratamento farmacológico , Fenômenos Biomecânicos , Cães , Esquema de Medicação , Coxeadura Animal , Dor/tratamento farmacológicoRESUMO
The objective of the present study was to evaluate the teratogenic potential of a novel oxygen-coordinated niacin-bound chromium complex (NBC) in Sprague-Dawley rats. Due to its potential to affect fat synthesis and reduce food intake, processes which are often crucial in normal fetal development, this teratology study was undertaken as part of a multi-generation reproductive investigation. The animals in this study were selected randomly after weaning from each F(2b) litter of the F1 generation from the two-generation reproductive toxicity study. To start the teratology study, Sprague-Dawley rat pups ( approximately 30/sex/group) from the F(2b) generation were allowed to grow up to 10-12 weeks of age before mating. The rats in treatment group were exposed directly to NBC through feed. The dietary exposure levels were the same as those employed for the two-generation reproductive toxicity study, viz. 4, 15, or 60 ppm. Following mating at maturity, the pregnant rats were observed daily for clinical signs of adverse effects, and body weight and feed consumption were recorded. On the day 20th of the gestation, animals were subjected to a necropsy and caesarean section to examine the uterus, ovaries and fetuses for assessment of different parameters of pregnancy and embryo-fetal defects. In this study, no indications of maternal toxicity, adverse effects on the parameters evaluated for the gravid uteri, external abnormalities in the fetuses, soft tissue abnormalities in the fetuses, or skeletal abnormalities in the fetuses were noted. Based on the results of this developmental toxicity study, NBC was found to benon-teratogenic in Sprague-Dawley rat, at the dietary exposure levels of 4, 15, and 60 ppm, equivalent to the dose levels of 0.50, 2.0, or 8.0mg/kg/day, respectively.
Assuntos
Anormalidades Induzidas por Medicamentos , Cromo/toxicidade , Niacina/análogos & derivados , Niacina/toxicidade , Compostos Organometálicos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
With a view to the rational design of selective quinoxaline derivatives, 2D and 3D-QSAR models have been developed for the prediction of anti-tubercular activities. Successful implementation of a predictive QSAR model largely depends on the selection of a preferred set of molecular descriptors that can signify the chemico-biological interaction. Genetic algorithm (GA) and simulated annealing (SA) are applied as variable selection methods for model development. 2D-QSAR modeling using GA or SA based partial least squares (GA-PLS and SA-PLS) methods identified some important topological and electrostatic descriptors as important factor for tubercular activity. Kohonen network and counter propagation artificial neural network (CP-ANN) considering GA and SA based feature selection methods have been applied for such QSAR modeling of Quinoxaline compounds. Out of a variable pool of 380 molecular descriptors, predictive QSAR models are developed for the training set and validated on the test set compounds and a comparative study of the relative effectiveness of linear and non-linear approaches has been investigated. Further analysis using 3D-QSAR technique identifies two models obtained by GA-PLS and SA-PLS methods leading to anti-tubercular activity prediction. The influences of steric and electrostatic field effects generated by the contribution plots are discussed. The results indicate that SA is a very effective variable selection approach for such 3D-QSAR modeling.
Assuntos
Algoritmos , Modelos Químicos , Quinoxalinas/química , Quinoxalinas/farmacologia , Desenho de Fármacos , Humanos , Modelos Genéticos , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Quinoxalinas/síntese químicaRESUMO
The objective of this study was to evaluate the effects of a novel oxygen-coordinated niacin-bound chromium(III) complex (NBC) on the reproductive systems of male and female rats, the postnatal maturation and reproductive capacity of their offspring, and possible cumulative effects through multiple generations. Sprague-Dawley rats were maintained on feed containing NBC at dose levels of 0, 4, 15, or 60ppm for 10weeks prior to mating, during mating, and, for females through gestation and lactation, across two generations. For the parents (F(0) and F(1)) and the offspring (F(1) and F(2a)), reproductive parameters such as fertility and mating, gestation, parturition, litters, lactation, sexual maturity and development of offspring were assessed. Results from the current study indicated that dietary exposure of NBC to parental male and female rats of both (F(0) and F(1)) the generations during the premating and mating periods, for both sexes, and during gestation and lactation in case of female rats, did not cause any significant incidence of mortality or abnormal clinical signs. Compared to respective controls, NBC exposure did not affect reproductive performance as evaluated by sexual maturity, fertility and mating, gestation, parturition, litter properties, lactation and development of the offspring. Based on the findings of this study, the parental as well as the offspring no-observed-adverse-effect level for NBC was determined to be greater than 60ppm in diet or equivalent to 7.80 and 8.31mg/kg body weight/day in male and female rats, respectively.
Assuntos
Cromo/toxicidade , Niacina/análogos & derivados , Niacina/toxicidade , Compostos Organometálicos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/fisiologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologiaRESUMO
The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that these supplements were well tolerated.
Assuntos
Condroitina/uso terapêutico , Colágeno Tipo II/uso terapêutico , Glucosamina/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Osteoartrite/veterinária , Animais , Condroitina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Glucosamina/administração & dosagem , Cavalos , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Dor/veterináriaRESUMO
BASP1 was detected in the embryonic and adult chicken lens, using immunological methods and by peptide sequence analysis. The protein was predominantly expressed in fiber cells and only faintly detected in annular pad cells. Localization of the protein was along the plasma membrane of fiber cells often in discrete areas. The role of BASP1 in the lens requires further study.
Assuntos
Proteínas do Olho/metabolismo , Cristalino/metabolismo , Proteínas de Membrana/metabolismo , Sequência de Aminoácidos , Animais , Membrana Celular/metabolismo , Embrião de Galinha , Galinhas , Proteínas do Olho/análise , Imunofluorescência , Cristalino/embriologia , Proteínas de Membrana/análise , Dados de Sequência MolecularRESUMO
ABSTRACT (-)-Hydroxycitric acid (HCA), a natural plant extract from the dried fruit rind of Garcinia cambogia, has been reported to inhibit fat synthesis and reduce food intake. The objective of this study was to evaluate the effects of a novel calcium/potassium salt of (-)-hydroxycitric acid (HCA-SX) on the reproductive systems of male and female rats, the postnatal maturation and reproductive capacity of their offspring, and possible cumulative effects through multiple generations. Sprague-Dawley rats (30/sex/group) were maintained on feed containing HCA-SX at dose levels of 0, 1000, 3000, or 10,000 ppm for 10 weeks prior to mating, during mating, and, for females, through gestation and lactation, across two generations. During the period of study, animals were examined daily for signs of clinical toxicity and their body weight and feed consumption were recorded twice a week. For the parents (F(0) and F(1)) and the offspring (F(1) and F(2a)), reproductive parameters such as fertility and mating, gestation, parturition, litters, lactation, sexual maturity, and development of offspring were assessed. At termination, necropsy and histopathological examinations were performed on all animals. Dietary exposure of HCA-SX to parental male and female rats of both (F(0) and F(1)) the generations during the premating and mating periods, for both sexes, and during gestation and lactation in case of female rats, did not reveal any remarkable incidence of mortality or abnormal clinical signs. Compared to respective controls, HCA-SX exposure did not affect feed consumption or body weight at any of the exposure levels. HCA-SX exposure did not affect reproductive performance as evaluated by sexual maturity, fertility and mating, gestation, parturition, litter properties, lactation, and development of the offspring. Based on the results of this study, the parental as well as the offspring no-observed-adverse-effect level for HCA-SX was determined to be greater than 10,000 ppm in diet or equivalent to 1018 and 1524 mg/kg body weight/day in male and female rats, respectively.
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ABSTRACT (-)-Hydroxycitric acid (HCA), active constituent (10%-30%) of the dried fruit rind of Garcinia cambogia, is commonly used as a dietary supplement for weight management. The objective of the present study was to evaluate the teratogenic potential of a novel calcium/potassium salt of HCA (HCA-SX) in Sprague-Dawley rats. Due to its potential to affect fat synthesis and reduce food intake, processes that are often crucial in normal fetal development, this teratology study was undertaken as part of a multigeneration reproductive investigation. The animals in this study were selected randomly after weaning from each F(2b) litter of the F(1) generation from the two-generation reproductive toxicity study. To start the teratology study, Sprague-Dawley rat pups ( approximately 30/sex/group) from the F(2b) generation were allowed to grow up to 10 to 12 weeks of age before mating. The rats in the treatment group were exposed directly to HCA-SX through feed, while prior to their weaning, they had indirect exposure to the test material during lactation. The dietary exposure levels were the same as those employed for the two-generation reproductive toxicity study, viz. 1000, 3000, or 10,000 ppm. Following mating at maturity, the pregnant rats were observed daily for clinical signs of adverse effects, and body weight and feed consumption were recorded. On day 20 of gestation, animals were subjected to a necropsy and cesarean section to examine the uterus, ovaries, and fetuses for assessment of different parameters of pregnancy and embryo-fetal defects. Despite a slight (13%) lowering of maternal body weight gain during gestation period in the group receiving 10,000 ppm HCA-SX, no evidence of maternal toxicity, adverse effects on the parameters evaluated for the gravid uteri, external abnormalities in the fetuses, soft tissue abnormalities in the fetuses, or skeletal abnormalities in the fetuses were noted. Based on the results of this developmental toxicity study, conducted in continuation of a two-generation reproductive toxicity study, HCA-SX was not found to be teratogenic in the Sprague-Dawley rat at the dietary exposure levels of 1000, 3000, and 10,000 ppm, equivalent to the dose levels of 103, 352, or 1240 mg/kg/day, respectively.
Assuntos
Citratos/administração & dosagem , Colágeno Tipo II/administração & dosagem , Doenças do Cão/tratamento farmacológico , Osteoartrite/veterinária , Administração Oral , Animais , Compostos de Cromo/administração & dosagem , Doenças do Cão/patologia , Cães , Quimioterapia Combinada , Osteoartrite/tratamento farmacológico , Dor/prevenção & controle , Dor/veterinária , Medição da Dor/veterinária , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Cataract is an age related disease of protein aggregation. It has been suggested that aging affects the cells ability to protect protein integrity. The protein integrity, which is essential for cellular homeostasis, is maintained by a complex system of refolding or degradation of damaged proteins. The heat shock proteins (hsps) are the major contributors in the maintenance of protein integrity. The heat shock transcription factor (HSF-1) is the master regulator of all hsp synthesis in response to stress. This investigation examined the role of HSF-1 in the regulation of hsp synthesis in early and late passaged alphaTN-4 cells. Data collected in this study revealed that the nucleotide sequence of HSF-1 mRNA obtained from early and late passaged alphaTN-4 cells were identical. When early and late passaged cell were exposed to thermal stress, their hsp expression were also similar. HSP-40 expression was detected after 2 h of heat stress, whereas HSP-70 and low molecular weight heat shock protein alphabeta crystallin showed significantly increased synthesis 18 h post heat stress. The late passaged alphaTN-4 cells ability to upregulate hsps in response to heat stress could be due to its high replicative activities. The data presented here suggests a relationship between the presence of functional HSF-1 and sustained proliferative activities of the late passaged alphaTN-4 cell.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Células Epiteliais/citologia , Proteínas de Choque Térmico/biossíntese , Temperatura Alta , Cristalino/citologia , Estresse Fisiológico , Fatores de Transcrição/fisiologia , Animais , Sequência de Bases , Proliferação de Células , Células Cultivadas , Células Epiteliais/metabolismo , Proteínas de Choque Térmico HSP40/biossíntese , Proteínas de Choque Térmico HSP70/biossíntese , Fatores de Transcrição de Choque Térmico , Cristalino/metabolismo , Camundongos , RNA Mensageiro , Fatores de Tempo , Regulação para CimaAssuntos
Implantação do Embrião , Hormônios Esteroides Gonadais/metabolismo , Comunicação Parácrina , Receptores de Ativinas Tipo I/metabolismo , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Decídua/efeitos dos fármacos , Decídua/metabolismo , Implantação do Embrião/genética , Feminino , Hormônios Esteroides Gonadais/farmacologia , Humanos , Fator Inibidor de Leucemia/imunologia , Metaloproteinases da Matriz Secretadas/metabolismo , Proteína Nodal , Gravidez , Progesterona/farmacologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
ABSTRACT This investigation was undertaken to evaluate the therapeutic efficacy and safety of glycosylated undenatured type II collagen (UC-II) alone or in combination with glucosamine HCl and chondroitin sulfate in arthritic dogs. Twenty dogs divided into four groups (n = 5) were daily treated orally for 120 days: group I, placebo; group II, 10 mg UC-II; group III, 2,000 mg glucosamine + 1,600 mg chondroitin; group IV, UC-II (10 mg) + glucosamine (2,000 mg) + chondroitin (1,600 mg), followed by a 30-day withdrawal period. On a monthly basis, dogs were examined for overall pain, pain upon limb manipulation, and exercise-associated lameness. Serum samples were analyzed for markers of liver function (ALT and bilirubin) and renal function (BUN and creatinine). Body weight was also measured at a monthly interval. Dogs in group I exhibited no change in arthritic conditions. Dogs receiving UC-II alone showed significant reductions in overall pain within 30 days (33%) and pain upon limb manipulation and exercise-associated lameness after 60 days (66% and 44%, respectively) of treatment. Maximum reductions in pain were noted after 120 days of treatment (overall pain reduction, 62%; pain reduction upon limb manipulation, 91%; and reduction in exercise-associated lameness, 78%). The overall activity of the dogs in the UC-II supplemented with glucosamine and chondroitin group (group IV) was significantly better than the glucosamine + chondroitin-supplemented group (group III). Glucosamine and chondroitin alleviated some pain, but in combination with UC-II (group IV) provided significant reductions in overall pain (57%), pain upon limb manipulation (53%), and exercise-associated lameness (53%). Following withdrawal of supplements, all dogs (groups II to IV) experienced a relapse of pain. None of the dogs in any groups showed any adverse effects or change in liver or kidney function markers or body weight. Data of this placebo-controlled study demonstrate that daily treatment of arthritic dogs with UC-II alone or in combination with glucosamine and chondroitin markedly alleviates arthritic-associated pain, and these supplements are well tolerated as no side effects were noted.
RESUMO
Experiments were performed to characterize a prominent nuclear matrix (NM) protein isolated from tissue cultured mouse lens epithelial cells. This NM protein was separated by SDS-PAGE and the stained gel band was analyzed by mass spectroscopy. Blast analysis of the amino acid sequence derived by mass spectroscopy revealed the presence of Lamin C in the NM of the mouse lens epithelial cells. We also examined nuclear proteins of adult and fetal human lenses. Data collected from these experiments showed the presence of Lamin C in both adult and fetal lens cells. However fetal lens cells only show Lamin C dimers, whereas adult human lens contained dimers, monomers and degraded Lamin C. Early and late passaged tissue cultured mouse lens epithelial cells also contained Lamin C in the nucleus with a preponderance of the dimer in the early passaged cells. The biological significance of the presence of dimers in human fetal lens cells and early passaged mouse lens cells is not known. However, it could suggest an enhanced docking capability of Lamin C dimers for other physiologically important nuclear proteins.
Assuntos
Células Epiteliais/metabolismo , Laminas/metabolismo , Cristalino/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Humanos , Immunoblotting , Lamina Tipo A/química , Lamina Tipo A/isolamento & purificação , Lamina Tipo A/metabolismo , Laminas/química , Laminas/isolamento & purificação , Cristalino/citologia , Camundongos , Dados de Sequência Molecular , Matriz Nuclear/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/isolamento & purificação , Proteínas Nucleares/metabolismo , Análise de Sequência de Proteína , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de TempoRESUMO
Over 35 million adults suffer from fatigue or lack of energy. In this study, we assessed the safety of a novel niacin-bound chromium-based Energy Formulation, which also contained caffeine, D-ribose, Withania somnifera extract, and selected amino acids. Niacin-bound chromium is a novel source of bioavailable chromium (III), and known to promote healthy lipid profile. Male and female Sprague-Dawley rats were fed 125 ppm Energy Formulation for 90 consecutive days. Body weight, feed, and water intake were monitored over the period of 90 days. No significant changes were observed between the control and treatment groups following subchronic supplementation with this Energy Formulation. Furthermore, no significant changes were observed in selected organ weights individually and as percentages of body and brain weights. The Energy Formulation supplementation did not cause changes in hepatic lipid peroxidation or DNA fragmentation after 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations revealed no adverse effects in the treatment group. These findings demonstrate the safety of this Energy Formulation.
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The weight-loss efficacy of a novel, water-soluble, calcium-potassium salt of (-)-hydroxycitric acid (HCA-SX) was re-examined in 90 obese subjects (BMI: 30-50.8 kg/m2). We combined data from two previously reported randomized, double-blind, placebo-controlled clinical studies in order to achieve a better statistical evaluation based on a larger population. This re-examination of data also allowed us to reflect more intensely on various aspects of weight loss studies. Subjects were randomly divided into three groups: group A received a daily dose of HCA-SX 4, 667 mg (providing 2,800 mg HCA per day); group B was given a daily dose of a combination of HCA-SX 4,667 mg, niacin-bound chromium (NBC) 4 mg (providing 400 microg elemental chromium), and Gymnema sylvestre extract (GSE) 400 mg (providing 100 mg gymnemic acid); and group C received a placebo in three equally divided doses 30-60 min before each meal. All subjects were provided a 2,000 kcal diet/day and participated in a supervised walking program for 30 min/day, 5 days/week. Eighty-two subjects completed the study. At the end of 8 weeks, in group A, both body weight and BMI decreased by 5.4%, low-density lipoprotein and triglycerides levels were reduced by 12.9% and 6.9%, respectively, while high-density lipoprotein levels increased by 8.9%, serum leptin levels decreased by 38%, serotonin levels increased by 44.5% and urinary excretion of fat metabolites increased by 32-109%. Group B demonstrated similar beneficial changes, but generally to a greater extent. No significant adverse effects were observed. The combined results confirm that HCA-SX and, to a greater degree, the combination of HCA-SX plus NBC and GSE reduce body weight and BMI, suppress appetite, improve blood lipid profiles, increase serum leptin and serotonin levels and increase fat oxidation more than placebo. We conclude that dosage levels, timing of administration, subject compliance and bioavailability of HCA-SX significantly affect results and that when taken as directed, HCA-SX is a highly effective adjunct to healthy weight control.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Cálcio/química , Citratos/uso terapêutico , Obesidade/tratamento farmacológico , Potássio/química , Adulto , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/química , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Cromo/administração & dosagem , Cromo/uso terapêutico , Citratos/administração & dosagem , Citratos/química , Método Duplo-Cego , Quimioterapia Combinada , Gymnema sylvestre/química , Humanos , Leptina/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Niacina/administração & dosagem , Niacina/uso terapêutico , Preparações de Plantas/administração & dosagem , Preparações de Plantas/uso terapêutico , Serotonina/sangue , Solubilidade , Resultado do TratamentoRESUMO
DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.
Assuntos
Colágeno Tipo II/uso terapêutico , Doenças do Cão/tratamento farmacológico , Osteoartrite/veterinária , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colágeno Tipo II/administração & dosagem , Creatinina/sangue , Doenças do Cão/sangue , Doenças do Cão/patologia , Cães , Coxeadura Animal , Osteoartrite/tratamento farmacológico , Medição da Dor/veterinária , Índice de Gravidade de Doença , Resultado do Tratamento , Ureia/sangueRESUMO
Abstract Each year more than 50 million Americans suffer from allergic rhinitis, which is a state of hypersensitivity or hyperimmunity. Basically, allergic rhinitis is symptomatically recognized as the inflammation and irritation of the nasal mucosal membranes; sneezing; stuffy/runny nose; nasal congestion; and itchy; watery, and swollen eyes; and defined as a state of hypersensitivity/ hyperimmunity caused by exposure to a particular allergen (antigen) that results in increased reactivity upon subsequent exposure. A novel polyherbal formulation (Aller-7/NR-A2) was developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants, including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum. Earlier studies in our laboratories have demonstrated potent antihistaminic, anti-inflammatory, antispasmodic, antioxidant, and mast-cell stabilization activities of Aller-7 in addition to its efficacy in a clinical setting. A series of preliminary toxicological evaluations were also conducted in the past, which demonstrated its safety. In this study, we have conducted further safety studies on Aller-7, including acute oral, acute dermal, acute dermal irritation, eye irritation, and 90-day repeated dose toxicity studies. Acute oral toxicity of Aller-7 was found to be greater than 5,000 mg/kg body weight in both male and female rats and no mortality or toxicity was observed at this dose, while the acute dermal toxicity was found to be greater than 2,000 mg/kg body weight. In the acute dermal irritation study, the skin irritancy index was found to be 0.0, which classifies Aller-7 as a nonirritant to rabbit skin. In the acute eye irritation study, Aller-7 was found to have minimal irritancy to eyes of rabbits. In the repeated-dose 90-day oral toxicity study, Aller-7 was administered at dose levels of 100, 300, and 1,000 mg/kg rat body weight for 90 consecutive days by oral gavage. Aller-7 did not induce any significant change in the hematological parameters. No ocular abnormalities were observed. Some minor histopathological changes were observed, but did not reveal any significant treatment-related histopathological changes. The above findings revealed that the no observed adverse effect level (NOAEL) of Aller-7 is greater than 1,000 mg/kg body weight. Taken together, these studies demonstrate the broad spectrum safety of Aller-7.
RESUMO
Allergic rhinitis is an immunological disorder and an inflammatory response of nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs when the body overreacts to a substance such as pollens or dust. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since inflammation is an integral mechanistic component of allergy, the present study aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats. The trypsin inhibitory activity of Aller-7 was also determined and compared with ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against compound 48/80-induced paw edema in Balb/c mice, while under the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7 significantly inhibited compound 48/80-induced paw edema at all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition against carrageenan-induced acute inflammation in Wistar Albino rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant-induced arthritis in Wistar Albino rats and an approximately 63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively. These results demonstrate that this novel polyherbal formulation is a potent anti-inflammatory agent that can ameliorate the symptoms of allergic rhinitis.