A Prospective Study on Prescription Pattern in Chronic Obstructive Pulmonary Disease.

Background: Irrational prescribing results produce a negative impact on health and economy of both individuals and society, leading to wastage of resources and widespread health hazards. Method: Outpatients with mild, moderate, and severe COPD were included. Several parameters were noted: patient's age and gender, outpatient (OPD) ID number, date of admission, occupation, h/o smoking, alcohol consumption, etc, disease condition details (duration, gradation as mild, moderate and severe, and co-existing diseases), prescribed medication details (dose, frequency, route of administration, and duration). Drug selection was assessed as per GOLD guidelines, the severity of disease was categorized according to the same guidelines, and medication efficacy was evaluated by treatment outcome according to the modified MRC dyspnoea scale. Results: Inhalation route (36.95%) was the most preferred route of drug administration in this study, followed by the parenteral route (34.34%), and enteral route (28.71%). Adherence to GOLD 2015: All patients (n=400) were categorized to Gold stages I to IV based on the severity of COPD. Amongst these patients, 11 were in stage I, 146 in stage II, 184 in stage III, and 59 in stage IV. The majority of subjects received fixed-dose combination therapy: levocetirizine + montelukast (77%) and least bromhexine + guaiphenesin + terbutaline + menthol (18%). Dyspnoea status was graded from 0 to 4 according to the modified MRC dyspnea scale. Out of the 400 patients, 18 had grade 0, 44 grade 1, 156 grade 2, 133 grade 3, and 49 grade 4. Conclusion: Overall, data from this analysis suggest that adherence to GOLD guidelines does not have a perceivable impact on symptom prevalence, exacerbation rate or lung function. Male sex, asthma and severe co-morbidities as a cerebrovascular insult could be associated with a risk for frequent exacerbations.

Diferuloylmethane augments the cytotoxic effects of piplartine isolated from Piper chaba.

Natural compound based anticancer drug discovery is gaining interest against a wide variety of tumors. E-piplartine (trans-piplartine), a natural compound isolated from Piper chaba roots is examined against rat histiocytoma (BC-8), mouse embryonal carcinoma (PCC4), mouse macrophages (P388D1 and J774), and human neuroblastoma (IMR32) tumor cells. While Z-piplartine (cis-piplartine) failed to induce cytotoxicity (even at higher concentrations, 50 microM), E-piplartine induced a dose-dependent cytotoxicity (2-24 microM) in different tumor cells. The combinatorial treatment of piplartine with diferuloylmethane (curcumin), an anti-inflammatory and anticancer agent, significantly enhanced the piplartine induced cytotoxicity in tumor cells. Diferuloylmethane itself is not cytotoxic at 15 microM concentration; however, potentiated the piplartine induced cytotoxicity. The tumor cell killing with piplartine is preceded by G1 cell cycle arrest, and surpassed diferuloylmethane induced G2/M arrest when used in combination. In PCC4 cells, piplartine inhibited the cell cycle progression by inactivating cdk2 and destabilizing cyclin D1, whereas diferuloylmethane combination inhibited the ERK1/2 and Raf-1 signaling in addition to the inhibition of cell cycle progression. The over expression of heat shock protein 70, Hsp70 in rat histiocytic tumor cells interfered with piplartine induced cytotoxicity, hence, a cross talk between stress response and anticancer agents is presented. Our data demonstrates the biological and medicinal importance of piplartine isolated from the roots of P. chaba, and indicates that E-piplartine may be a promising candidate to use in combinatorial treatments to combat cancer.

Heat shock transcription factors regulate heat induced cell death in a rat histiocytoma.

Heat shock response is associated with the synthesis of heat shock proteins (Hsps) which is strictly regulated by different members of heat shock transcription factors (HSFs). We previously reported that a rat histiocytoma, BC-8 failed to synthesize Hsps when subjected to typical heat shock conditions (42 degrees C, 60 min). The lack of Hsp synthesis in these cells was due to a failure in HSF1 DNA binding activity. In the present study we report that BC-8 tumor cells when subjected to heat shock at higher temperature (43 degrees C, 60 min) or incubation for longer time at 42 degrees C, exhibited necrosis characteristics; however,under mild heat shock (42 degrees C, 30 min) conditions cells showed activation of autophagy. Mild heat shock treatment induced proteolysis of HSF1, and under similar conditions we observed an increase in HSF2 expression followed by its enhanced DNA binding activity. Inhibiting HSF1 proteolysis by reversible proteasome inhibition failed to inhibit heat shock induced autophagy. Compromising HSF2 expression but not HSF1 resulted in the inhibition of autophagy, suggesting HSF2 dependent activation of autophagy. We are reporting for the first time that HSF2 is heat inducible and functions in heat shock induced autophagic cell death in BC-8 tumor cells.