Safety evaluation of standardized Ayurvedic formulation-Panchvalkala, by subacute toxicity study.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala is a conventional Ayurvedic medicine used as a douche in gynecological disorders such as leucorrhea, infertility, and endometriosis. Recently, we have reported the anticancer activity of Panchvalkala aqueous extract (PVaq) in cervical cancer cell lines, SiHa (HPV16+), HeLa (HPV18+), and mouse papilloma models. AIM OF THE STUDY: Here, we have evaluated the safety of the aqueous extract of Ayurvedic formulation, Panchvalkala (PVaq), in Swiss albino mice by performing subacute toxicity study. MATERIALS AND METHODS: Male and female Swiss albino mice (n = 5/sex/group) were gavaged orally with different doses of PVaq for 28 consecutive days. The mice were distributed into six groups: I (vehicle control), II (vehicle control reversal), III (PVaq 250 mg/kg), IV (PVaq 500 mg/kg), V (1000 mg/kg) and VI (1000 mg/kg high dose reversal). Animals were observed periodically to record any clinical signs of toxicity or mortality. After completion of treatment and recovery periods, animals were evaluated for the effect of PVaq on urine parameters, followed by hematological and biochemical parameters. Animals were sacrificed on day 29 for gross observation of vital organs and to study their histopathology. Reversal groups were maintained for further 14 days to observe any delayed onset of toxic side effects or reversal of toxicity, followed by sacrificing the mice on day 43. RESULTS: In the subacute toxicity study, PVaq did not show any significant change in food, water consumption, and body weights. There were no significant alterations in hematology, biochemistry, urine parameters, and histopathology of the analyzed tissues (brain, heart, liver, lung, spleen, thymus, kidney, epididymis/ovaries, and testis/uterus). The parameters were comparable to their respective controls in both the female as well as the male mice groups. Upon macroscopic and microscopic observation of vital organs, no abnormality was detected compared to the respective control groups. CONCLUSION: The subacute toxicity study demonstrated that oral administration of PVaq was safe in female and male Swiss albino mice.

Panchvalkala, a traditional Ayurvedic formulation, exhibits antineoplastic and immunomodulatory activity in cervical cancer cells and C57BL/6 mouse papilloma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala, an Ayurvedic traditional formulation has references in Charak Samhita and Bhavaprakasha Nighantu for the treatment of women with endometriosis-related problems, leucorrhea and vaginal ailments. The formulation comprises of equal ratios of the barks from Ficus glomerata, Ficus virens, Ficus religiosa, Ficus benghalensis, and Thespesia populnea. AIM OF THE STUDY: The present study aimed to evaluate the anticancer and immunomodulatory activity of aqueous extract of Panchvalkala (PVaq) against cervical cancer in vitro and in vivo. MATERIALS AND METHODS: The effect of PVaq on disruption of mitochondrial membrane potential in cervical cancer cell lines, SiHa and HeLa, was studied by using JC1 dye. The expression of generic caspases in the cells after treatment with PVaq was evaluated by ELISA kit. The expression of pRb, p53, E6 and E7 proteins were evaluated by western blotting. Acute oral toxicity and DRF studies were performed in Swiss albino mice by following OECD guidelines 423 and 407, respectively. Tumor retardation study was done in C57BL/6 mouse papilloma model. The mice were divided into six groups: No tumor control (NTC), Tumor control (TC), Cisplatin (Cis) (4 mg/kg b.w.), PVaq 100, 200 mg/kg b.w and combination of PVaq (200 mg/kg b.w.) and Cisplatin (4 mg/kg b.w.). The mice were orally gavaged with PVaq daily for 14 days and cisplatin was given intravenously on every 1st, 5th and 9th day. Hematological and biochemical parameters were studied by using hematology analyzer and kits, respectively. E6 and E7 gene expression in the tumor samples was determined by qPCR. Th1 and Th2 cytokine levels were determined by ELISA. RESULTS: PVaq induced mitochondrial depolarization in SiHa and HeLa, and increased the expression of generic caspases, resulting into apoptosis. PVaq upregulated the expression of tumor suppressor proteins (p53 and pRb) and reduced the expression of viral oncoproteins (E6 and E7). Acute toxicity study displayed non-toxicity of PVaq while DRF study ensured its safe dose for further efficacy studies. PVaq reduced tumor volume and weight in mouse papilloma model and induced immunomodulation in the animals. It increased serum levels of IL-2 (Th1) with a concomitant decrease in IL-10 (Th2) cytokines. The drug did not affect body weight, food consumption and organ histopathology of the animals. CONCLUSIONS: PVaq exhibited anticancer and immunomodulatory activities against cervical cancer cells and female mouse papilloma model.

Tremor retrainment as therapeutic strategy in psychogenic (functional) tremor.

BACKGROUND: Entrainment, the change or elimination of tremor as patients perform a voluntary rhythmical movement by the unaffected limb, is a key diagnostic hallmark of psychogenic tremor. OBJECTIVE: To evaluate the feasibility of using entrainment as a bedside therapeutic strategy ('retrainment') in patients with psychogenic tremor. METHODS: Ten patients with psychogenic tremor (5 women, mean age, 53.6 ± 12.8 years; mean disease duration 4.3 ± 2.7 years) were asked to participate in a pilot proof-of-concept study aimed at "retraining" their tremor frequency. Retrainment was facilitated by tactile and auditory external cueing and real-time visual feedback on a computer screen. The primary outcome measure was the Tremor subscale of the Rating Scale for Psychogenic Movement Disorders. RESULTS: Tremor improved from 22.2 ± 13.39 to 4.3 ± 5.51 (p = 0.0019) at the end of retrainment. The benefits were maintained for at least 1 week and up to 6 months in 6 patients, with relapses occurring in 4 patients between 2 weeks and 6 months. Three subjects achieved tremor freedom. CONCLUSIONS: Tremor retrainment may be an effective short-term treatment strategy in psychogenic tremor. Although blinded evaluations are not feasible, future studies should examine the long-term benefits of tremor retrainment as adjunctive to psychotherapy or specialized physical therapy.

A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival: a comparative study with human parathyroid hormone.

PURPOSE: 6-C-ß-D-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF) is a novel compound isolated from Ulmus wallichiana, reported to have bone anabolic action in ovariectomized rats. Here, we studied the effect of GTDF in glucocorticoid (GC)-induced bone loss and its mode of action. METHODS: Osteoblasts were cultured from rat calvaria or bone marrow to study apoptosis and differentiation by dexamethasone (Dex), methylprednisolone (MP), GTDF, quercetin and rutin. Female Sprague Dawley rats were treated with Dex or MP with or without GTDF or PTH. Efficacy was evaluated by bone microarchitecture using microcomputed tomography, determination of new bone formation by fluorescent labeling of bone and osteoblast apoptosis by co-labeling bone sections with Runx-2 and TUNEL. Serum osteocalcin was determined by ELISA. RESULTS: GTDF preserved trabecular and cortical bones in the presence of Dex and MP and mitigated the MP-mediated suppression of serum osteocalcin. Co-administration of GTDF to MP rats increased mineral apposition, bone formation rates, bone biomechanical strength, reduced osteoblast apoptosis and increased osteogenic differentiation of bone marrow stromal cells compared to MP group, suggesting in vivo osteogenic effect of GTDF. These effects of GTDF were to a great extent comparable to PTH. GTDF prevented GC-induced osteoblast apoptosis by inhibiting p53 expression and acetylation, and activation of AKT but did not influence transactivation of GC receptor (GR). CONCLUSIONS: GTDF protects against GC-induced bone loss by promoting osteoblast survival through p53 inhibition and activation of AKT pathways but not as a GR antagonist. GTDF has the potential in the management of GC-induced osteopenia.

Employee suggestion programs: the rewards of involvement.

Successful ESPs are the products of a great deal of effort by managers, administrators, teams, individuals, and reviewers, who are all striving to achieve the goals of increased profitability and enhanced employee involvement. A review of the literature indicates that there are several prescriptions that will increase the likelihood of a successful ESP (see the box). Today's American business prophets sound ceaseless calls to arms in the name of "world class performance," "global competitiveness," "total quality management," and a variety of other buzz terms. A burgeoning industry has evolved that promises, through speeches, teleconferences, seminars, and consulting contracts, to teach American organizations how to achieve excellence. In the face of a sputtering economy and unrelenting competitive pressure, today's managers must translate these laudatory ideals into hands-on reality without sacrificing the firm's profit margin to experimentation. If any idea can help an organization achieve improvement through a workable program, then that idea and that program deserve real consideration. An ESP represents an opportunity to tap the intelligence and resourcefulness of an organization's employees, and by doing so, reap significant cost savings. Those companies and managers that have an ESP program uniformly list economic advantages first when describing the benefits of their employee suggestion programs. But there is another deeper and longer term benefit inherent in an ESP. These programs allow employees to become involved in their organization; they drive deaccession to lower levels, they give employees more responsibility, they foster creative approaches to work, and they encourage creativity in pursuit of company goals.(ABSTRACT TRUNCATED AT 250 WORDS)