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Effect of spices on lipid metabolism in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

Colon cancer is the second most common cancer among men and women worldwide. We investigated the effect of red chilli (Capsicum annum L.), cumin (Cuminum cyminum L.), and black pepper (Piper nigrum L.) on colon cancer induced in rats by a colon-specific carcinogen, 1,2-dimethylhydrazine (DMH). Colon cancer was induced by subcutaneous injection of DMH at a dosage of 20 mg/kg of body weight (15 doses, at 1-week intervals). The rats were continued with the standard pellet diet and supplemented red chilli [C. annum L., 0.015% (wt/wt) mixed with the diet], cumin seeds [C. cyminum L., 1.25% (wt/wt) mixed with the diet], and black pepper (P. nigrum L., 0.5% (wt/wt) mixed with the diet] throughout the experimental period. After the total experimental period of 32 weeks (including 2 weeks of acclimatization) the incidence and number of tumors in the colon were observed to be significantly higher in the rats administered DMH and/or red chillis, as compared with the cumin + DMH and black pepper + DMH groups. No tumors were observed in the control, cumin + DMH, or black pepper + DMH groups. The levels of fecal bile acids and neutral sterols in 24-hour fecal samples were significantly decreased in DMH + chilli-administered rats, while the excretion of fecal bile acids and neutral sterols was significantly increased in cumin + DMH- and black pepper + DMH-administered rats. In DMH-, chilli-, and chilli + DMH-administered rats the levels of cholesterol, cholesterol/phospholipid ratio, and 3-hydroxy-3-methylglutaryl-CoA reductase activity were decreased in cumin + DMH- and black pepper + DMH-treated rats. The phospholipid levels were reduced in the DMH, chilli, and chilli + DMH groups as compared with the cumin + DMH and black pepper + DMH groups. Our results show that chilli supplementation promotes colon carcinogenesis, whereas cumin or black pepper suppresses colon carcinogensis in the presence of the procarcinogen DMH.

1,2-Dimethylhydrazine↗

Processing of the 3' sequence extensions upon the 5S rRNA of a mutant yeast in Xenopus laevis germinal vesicle extract.

A processing endonuclease acts to remove a short sequence from the 3' end of transcripts of the Saccharomyces cerevisiae 5S ribosomal RNA gene in generating the mature sequence of 5S RNA. Cells bearing the nuclear mutation rna82 .1 lack this activity and accumulate 5S forms with additional nucleotides at their 3' termini. 5S RNAs labelled during short pulse- labellings of the mutant are essentially primary transcripts that mostly have the sequence U-U-A-U-U-U-C[U-U-U-U(U-U)] added to the 3' end of normal yeast 5S RNA. They are subjected in vivo to a series of slow processing events whereby this sequence is ultimately replaced by: U-U(A)1-9 in a substantial proportion of the 5S RNA molecules of the mutant [Piper, P. W., Bellatin , J. A. and Lockheart , A. (1983) EMBO J. 2, 353-359]. In higher eukaryotes no endonuclease cleavage occurs during 5S RNA maturation, yet processing at the 3' ends of certain transcripts made by RNA polymerase III, most notably transfer RNA precursors, is still important. Since the enzymes involved in this processing have not been well characterised, we investigated how the additional sequences upon rna82 .1 yeast 5S RNA are processed in vitro in a system from a higher eukaryote that is often used for studying transcription by RNA polymerase III, the Xenopus laevis germinal vesicle extract. Our results are consistent with slow digestion of these 5S molecules by a 3'----5' exonuclease until they become 122-123 nucleotides in length, whereupon digestion ceases. This activity probably participates in the processing of certain Xenopus RNA polymerase III transcripts.

Animals↗

The plasma membrane of yeast acquires a novel heat-shock protein (hsp30) and displays a decline in proton-pumping ATPase levels in response to both heat shock and the entry to stationary phase.

Recent studies have revealed that the action of the proton-translocating ATPase of the plasma membrane of yeast is an important determinant of several stress tolerances and affects the capacity of cells to synthesise heat shock proteins in response to heat shock [Panaretou, B. & Piper, P. W. (1990) J. Gen. Microbiol. 136, 1763-1770; Coote, P. J., Cole, M. B. & Jones, M. V. (1991) J. Gen. Microbiol. 137, 1701-1708]. This study investigated the changes to the protein composition of the Saccharomyces cerevisiae plasma membrane that result from a heat shock to dividing cultures and the entry to stationary growth caused by carbon source limitation. Plasma membranes were prepared from exponential, heat-shocked and stationary yeast cultures. The proteins of these membrane preparations were then analysed by polyacrylamide gel electrophoresis and immunoblot measurement of ATPase levels. The protein composition of plasma membranes displayed two prominent changes in response to both heat shock and the entry to stationary phase: (a) a reduction in the level of the plasma membrane ATPase; and (b) the acquisition of a previously uncharacterised 30 kDa heat-shock protein (hsp30). The ATPase decline with heat shock probably exerts an important influence over the ability of the cell to maintain ATPase activity, and therefore intracellular pH, during extended periods of stress. Through in vivo pulse-labelling of plasma membrane proteins synthesised before and during heat shock, followed by subcellular fractionation, it was shown that hsp30 is the only protein induced by the yeast heat-shock response that substantially copurifies with plasma membranes. It might therefore exert a stress-protective function specifically at this membrane.

Cell Membrane↗

Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression.

Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be improved by treatment with depigmenting agents. In the present study, piperlonguminine from Piper longum was discovered to inhibit melanin production in melanoma B16 cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH), 3-isobutyl-1-methylxanthine or protoporphyrin IX, where the compound exhibited stronger depigmenting efficacy than kojic acid. However, piperlonguminine did not affect 1-oleoyl-2-acetyl-sn-glycerol-induced melanogenesis and did not affect protein kinase C-mediated melanin production. Surprisingly, piperlonguminine did not inhibit the catalytic activity of cell-free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA expression. This effect was attributed to the inhibitory action of piperlonguminine on alpha-MSH-induced signaling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia-associated transcription factor, a key activator of the tyrosinase promoter. This study demonstrates that piperlonguminine is an efficient depigmenting agent with a novel mechanism of action.

1-Methyl-3-isobutylxanthine↗

The Saccharomyces cerevisiae weak-acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism.

Growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid results in the induction of the ATP-binding cassette (ABC) transporter Pdr12 in the plasma membrane (P. Piper, Y. Mahe, S. Thompson, R. Pandjaitan, C. Holyoak, R. Egner, M. Muhlbauer, P. Coote, and K. Kuchler, EMBO J. 17:4257-4265, 1998). Pdr12 appears to mediate resistance to water-soluble, monocarboxylic acids with chain lengths of from C(1) to C(7). Exposure to acids with aliphatic chain lengths greater than C(7) resulted in no observable sensitivity of Deltapdr12 mutant cells compared to the parent. Parent and Deltapdr12 mutant cells were grown in the presence of sorbic acid and subsequently loaded with fluorescein. Upon addition of an energy source in the form of glucose, parent cells immediately effluxed fluorescein from the cytosol into the surrounding medium. In contrast, under the same conditions, cells of the Deltapdr12 mutant were unable to efflux any of the dye. When both parent and Deltapdr12 mutant cells were grown without sorbic acid and subsequently loaded with fluorescein, upon the addition of glucose no efflux of fluorescein was detected from either strain. Thus, we have shown that Pdr12 catalyzes the energy-dependent extrusion of fluorescein from the cytosol. Lineweaver-Burk analysis revealed that sorbic and benzoic acids competitively inhibited ATP-dependent fluorescein efflux. Thus, these data provide strong evidence that sorbate and benzoate anions compete with fluorescein for a putative monocarboxylate binding site on the Pdr12 transporter.

ATP-Binding Cassette Transporters↗

Positive and negative contractile effects of neuropeptide Y on ventricular cardiomyocytes.

The potency of neuropeptide Y (NPY) to cause negative and positive contractile responses in rat ventricular cardiomyocytes was investigated. In these cells, NPY was found to activate the transient outward K+ current (Ito) and the slow inward Ca2+ current (Isi). As reported before (H. M. Piper, B. C. Millar, and J. R. McDermott, Naunyn Schmiedeberg's Arch. Pharmacol. 340: 333-337, 1989), NPY attenuated the increase in the contractile response induced by isoprenaline (10(-7) M). This effect of NPY could be abolished by 1) the presence of the inhibitor of Ito, 4-aminopyridine (4-AP, 0.5 mM); 2) pretreatment of the cells with pertussis toxin (1 microgram/ml for 6 h); and 3) the presence of the 19-amino acid COOH-terminal fragment of NPY, NPY-(18-36) (10(-6) M). In the absence of isoprenaline, but in the presence of 4-AP, NPY exerted a stimulatory effect on the cardiomyocytes. This effect could be abolished 1) by using the inhibitor of the Isi, verapamil (10(-8) M), but not 2) by pretreatment with pertussis toxin, nor 3) by coincubation with NPY-(18-36). The results indicate that in the rat the antiadrenergic negative contractile effect of NPY results from its action on the Ito. Blockade of this current by 4-AP unmasks a positive contractile effect of NPY that is related to activation of the Isi.

4-Aminopyridine↗

Disintegration of cytoskeletal structure of actin filaments in energy-depleted endothelial cells.

In a previous study [Watanabe, H., W. Kuhne, R. Spahr, P. Schwartz, and H. M. Piper. Am. J. Physiol. 260 (Heart Circ. Physiol. 29): H1344-H1352, 1991] metabolic inhibition (5 mM KCN + 5 mM 2-deoxy-D-glucose, for 2 h) was found to cause disintegration of F-actin filaments, cell retraction, and augmented paracellular macromolecule permeability in monolayer cultures of porcine aortic endothelial cells after a rapid depletion of ATP stores (90% in 5 min). These changes were reversible. In the present study, the nature of this cytoskeletal disintegration was investigated. 1) Disintegration of F-actin filaments within 2-h incubation under metabolic inhibition was accompanied by appearance of F-actin clumps in the cells, but total contents of F-actin remained unaltered. 2) Cytosolic Ca2+ levels rapidly rose in metabolically inhibited cells; after 2 h a 10-fold increase was observed. 3) Presence of the Ca2+ ionophore A23187 (10 microM) mimicked the reversible effect of metabolic inhibition on F-actin filaments and monolayer permeability but not the extensive depletion of ATP stores. 4) Existence of the Ca(2+)-activatable actin-severing protein gelsolin in endothelial cells was demonstrated. The results show that during the reversible phase of endothelial energy depletion disintegration of F-actin filaments is only partial, since it is based on their fragmentation and not depolymerization. Increase in cytosolic Ca2+ levels seems to be the primary cause for the fragmentation, possibly through the activation of gelsolin.

Actins↗

Importance of sodium for recovery of calcium control in reoxygenated cardiomyocytes.

The role of Na+ in the recovery from severe anoxic Ca2+ overload was investigated in isolated quiescent ventricular cardiomyocytes from adult rat. Changes of cytosolic Ca2+ and Na+ concentrations were followed by the fura 2 and Na(+)-binding benzofuran isophthalate techniques, respectively. When the fura 2 ratio (340/380 nm) reached saturation in anoxic cells, indicating a severe cytosolic Ca2+ overload, the cells were reoxygenated. This caused a rapid initial drop of cytosolic Ca2+ to a lower but still elevated level (phase I), followed by oscillatory Ca2+ transients at this level (phase II) and, within 10 min, the reestablishment of a stable cytosolic Ca2+ concentration at the normal resting level (phase III). As previously shown [B. Siegmund, R. Zude, and H. M. Piper. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1262-H1269, 1992], Ca2+ shifts in phase I and II are mainly due to uptake and release of Ca2+ by the sarcoplasmic reticulum. Phase I was unchanged, and phase II was much prolonged (> 60 min) in cells reoxygenated under Na+ pump inhibition (0.2 mM ouabain) or Na+ depletion. Phase III could only be reestablished (< 10 min) when ouabain was eluted or external Na+ replenished, respectively. The results show that full recovery of cytosolic Ca2+ control (phase III) requires an active sarcolemmal Na+ pump and the availability of external Na+. This indicates that phase III is determined by the transsarcolemmal extrusion of Ca2+ by a tandem mechanism consisting of 1) the Na+ pump, generating an extracellular-to-intracellular Na+ gradient, and 2) the sarcolemmal Na+/Ca2+ exchange, driven by that gradient to extrude Ca2+.

Animals↗

Feasibilty of a sleep intervention during adjuvant breast cancer chemotherapy.

PURPOSE/OBJECTIVES: To evaluate the feasibility of an intervention designed to promote sleep and modify fatigue during four cycles of adjuvant breast cancer chemotherapy. DESIGN: Prospective, repeated measures, quasi-experimental feasibility study. SETTING: Midwestern urban oncology clinics. SAMPLE: 25 women between the ages of 40-65 (mean = 54.3) with stage I-II breast cancer receiving doxorubicin-based chemotherapy. METHODS: Each woman developed, reinforced, and revised an individualized sleep promotion plan (ISPP) with four components: sleep hygiene, relaxation therapy, stimulus control, and sleep restriction techniques. A daily diary, the Pittsburgh Sleep Quality Index, a wrist actigraph, and the Piper Fatigue Scale were used to collect data two days before and seven days after each treatment. MAIN RESEARCH VARIABLES: Adherence, sleep and wake outcomes, and fatigue. FINDINGS: Adherence rates with the components of the ISPP varied during treatments one through four: sleep hygiene (68%-78%), relaxation therapy (57%-67%), stimulus control (46%-67%), and sleep restriction (76%-80%). Mean sleep and wake outcomes at baseline, peak, and rebound times were that (a) sleep latency remained brief (less than 30 minutes per night), (b) time awake after sleep onset exceeded the desired less than 30 minutes per night, (c) sleep efficiency scores remained stable at 85%-90%, (d) total rest time remained stable at 8-10 hours per night, (e) subjective ratings of feelings on arising were stable, and (f) nighttime awakenings were 8-10 per night. Fatigue outcomes were that fatigue was stable two days after each treatment and mean daily fatigue intensity was lower at treatment three than at treatment one but rebounded at treatment four. CONCLUSIONS: The intervention was feasible, adherence rates improved over time, and most sleep and wake patterns were consistent with normal values. Revisions will focus on decreasing nighttime awakenings. IMPLICATIONS FOR NURSING: Adopting behaviors to promote sleep may assist in maintaining sleep and managing fatigue during chemotherapy.

Adult↗

Adherence, sleep, and fatigue outcomes after adjuvant breast cancer chemotherapy: results of a feasibility intervention study.

PURPOSE/OBJECTIVES: To evaluate outcomes of an intervention designed to promote sleep and modify fatigue after adjuvant breast cancer chemotherapy. DESIGN: Prospective, repeated measures, quasi-experimental, feasibility study. SETTING: Midwestern urban oncology clinics. SAMPLE: 21 female participants, ages 43-66 years (meanX = 55.3) with stage I or II breast cancer status post four cycles of doxorubicin chemotherapy. Eight had four additional cycles of paclitaxel, 10 also had radiation, and 18 took tamoxifen. METHODS: each woman continued to revise her Individualized Sleep Promotion Plan (ISPP), developed during her first cycle of chemotherapy, that included sleep hygiene, relaxation therapy, stimulus control, and sleep restriction components. The daily diary, Pittsburgh Sleep Quality Index, wrist actigraph, and Piper Fatigue Scale were used for seven days 30, 60, and 90 days after the last chemotherapy treatment and one year after the first chemotherapy treatment. MAIN RESEARCH VARIABLES: Adherence and sleep and wake, fatigue, and ISPP components. FINDINGS: Adherence to the ISPP components remained high at all times (77%-88%) except for stimulus control (36%-56%). Sleep outcome means and the actigraph revealed that (a) sleep latency remained less than 30 minutes per night, (b) the time awake after sleep onset exceeded the desired less than 30 minutes per night, (c) sleep efficiency scores ranged from 82%-92%, (d) total rest time ranged from seven to eight hours per night, (e) feelings on arising ranged from 3.7-3.8 (on a 0-5 scale), (f) nighttime awakenings ranged from 10-11 per night, and (g) daytime naps ranged from 10-15 minutes in length. Fatigue remained low, from 2.9-3.5 on a 0-10 scale. CONCLUSIONS: Adherence rates remained high for most components. Sleep and wake patterns were within normal limits except for the number and duration of night awakenings. Fatigue remained low. IMPLICATIONS FOR NURSING: Future testing using an experimental design will focus on increasing ISPP adherence and decreasing nighttime awakenings. Adopting behavioral techniques to promote sleep may result in improved sleep and lower fatigue after chemotherapy.

Adult↗

Larvicidal effect of pepper plants on Aedes aegypti (L.) (Diptera: Culicidae).

Ethanolic extracts derived from three species of the Piperaceae (pepper) family, Piper longum L., P. ribesoides Wall., and P. sarmentosum Roxb. ex Hunt., were evaluated for efficacy against early 4th instar larvae of Aedes aegypti mosquitoes using larvicidal bioassays. The highest larvicidal efficacy was established from P. longum, followed by P. sarmentosum and P. ribesoides, with LC50 values of 2.23, 4.06, and 8.13 ppm, respectively. Observations of morphological alterations on treated 4th instar larvae revealed that most organs, except anal papillae, had a normal structural appearance that was similar to controls. Under light microscopy, the internal structures of anal papillae in the treated larvae showed shrinkage, while the external features were normal in appearance. Ultrastructural studies, however, clearly demonstrated external destruction, with extensive damage and shrunken cuticle of the anal papillae. The structural deformation of anal papillae probably led to their dysfunction, which may be intrinsically associated with the death of the larvae. This study affords some evidence regarding the action site of the pepper extracts and suggests their potential in developing new types of larvicides used for mosquito control.

Aedes↗

Protection of stored maize against Sitophilus zeamais (Motsch.) by use of essential oils of spices from Cameroon.

In storage, maize as other cereals is currently attacked by insects. The main specie present in Cameroon is Sitophilus zeamais (Coleop. Curculionidae). The popular way to prevent its damages is the use of synthetic insecticides. These chemicals extend their activities to non target animals. They are potentially dangerous for consumers and are implicated in the pollution of the environment. The development of products killing pests which are consumer-friendly is to be improved. In this respect, the use of essential oils from spices and aromatic plants could help. Six essential oils were tested, 3 are causes of high insect mortality. Xylopia aethiopica Dunal (Anonaceae) killed 97% of adults weevils and Ocimum gratissimum, (L.) (Lamiaceae) 74% after 4 days after ingestion. Piper nigrum (L.) (Piperaceae) killing more than 96% of weevil 48 hours after the contact. The potential of these non toxic products to protect stored maize against attacks of S. zeamais is hereby appraised.

Animals↗

In vitro screening of five local medicinal plants for antibacterial activity using disc diffusion method.

Medicinal plants have many traditional claims including the treatment of ailments of infectious origin. In the evaluation of traditional claims, scientific research is important. The objective of the study was to determine the presence of antibacterial activity in the crude extracts of some of the commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this preliminary investigation, the leaves were used and the crude extracts were subjected to screening against five strains of bacteria species, Methicillin Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol of Disc Diffusion Method (DDM). The antibacterial activities were assessed by the presence or absence of inhibition zones and MIC values. M. citrifolia, P. sarmentosum and C. asiatica methanol extract and A. paniculata (water extract) have potential antibacterial activities to both gram positive S. aureus and Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested showed antibacterial activities to gram negative E. coli and K. pneumoniae, except for A. paniculata and P. sarmentosum which showed activity towards P. aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding forms a basis for further studies on screening of local medicinal plant extracts for antibacteria properties.

Anti-Bacterial Agents↗

Bactericidal activity of black pepper, bay leaf, aniseed and coriander against oral isolates.

Present investigation focused on antibacterial potential of aqueous decoction of black pepper (Piper nigrum L.), bay leaf (Laurus nobilis L.), aniseed (Pimpinella anisum L.), and coriander (Coriandum sativum L.) against 176 bacterial isolates belonging to 12 different genera of bacterial population isolated from oral cavity of 200 individuals. The disc diffusion technique was employed. Overall aqueous decoction of black pepper was the most bacterial-toxic exhibited 75% antibacterial activity as compared to aqueous decoction of bay leaf (53.4%) and aqueous decoction of aniseed (18.1%), at the concentration of 10 ml/disc. The aqueous decoction of coriander did not show any antibacterial effect against tested bacterial isolates.

Adolescent↗

Differences in fatigue by treatment methods in women with breast cancer.

PURPOSE/OBJECTIVES: To investigate the differences between various cancer therapies (radiation, hormonal, chemotherapy, and their combinations) and the specific dimensions of fatigue (affective meaning, behavioral/severity, cognitive/mood, and sensory). DESIGN: Descriptive, cross-sectional, mailed survey design. SAMPLE AND SETTING: Data were collected from women who were breast cancer survivors and members of a nonprofit educational organization in the North-east. Criteria for this study included no self-reported disease recurrence, and treatment was within 18 months prior to the mailed survey (N = 322). The typical participant was middle-aged (mean = 52.2; SD = 10.3), Caucasian (93%), postmenopausal (55%), and diagnosed with cancer 2.42 (SD = 2.6) years prior to the study. METHODS: Secondary data analysis from a study using the Piper Fatigue Scale. VARIABLES: Level of fatigue. FINDINGS: Significant differences were found by treatment in total fatigue scores (p < 0.03) and cognitive/mood scores (p < 0.05). Women who received combination therapy had the highest fatigue scores (mean = 4.8; SD = 2.0); those who received only radiation therapy had the lowest fatigue scores (mean = 2.7; SD = 2.0). CONCLUSIONS: Fatigue in breast cancer survivors varies by type of cancer therapy. Future studies are needed to investigate the relationships between fatigue and hormonal therapy, and they need to be designed to examine changes over time. IMPLICATIONS FOR NURSING PRACTICE: Study findings advance knowledge about fatigue in women with breast cancer and aid nurses in providing anticipatory guidance for women undergoing different treatment regimens.

Adult↗

A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease.

BACKGROUND: Fatigue is a commonly encountered symptom of human immunodeficiency virus (HIV) disease, associated with significant psychological and functional morbidity and poor quality of life. Preliminary studies on the treatment of fatigue from the cancer and multiple sclerosis literature suggest that psychostimulants may be effective in reducing fatigue. OBJECTIVE: To compare the efficacy of 2 psychostimulant medications, methylphenidate hydrochloride (Ritalin) and pemoline (Cylert), with a placebo intervention for the treatment of fatigue in patients with HIV disease. METHODS: In this double-blind trial, 144 ambulatory patients with HIV disease and persistent and severe fatigue were randomized to treatment with methylphenidate, pemoline, or placebo. Medications were titrated up to a maximum dose of 60 mg of methlyphenidate hydrochloride, 150 mg of pemoline, or 8 capsules of placebo daily. Fatigue was measured using 2 self-reported rating scales, the Piper Fatigue Scale (PFS) and the Visual Analogue Scale for Fatigue (VAS-F). We also used the timed isometric unilateral straight leg-raising task, a measure of muscular endurance. Quality-of-life and psychological well-being measures included the Beck Depression Inventory, the Brief Symptom Inventory, and the 36-Item Short-Form Medical Outcomes Study Health Status Survey. Side effects were monitored using the Systematic Assessment for Treatment Emergent Events and the Extra-pyramidal Symptom Rating Scale. All measures were rated weekly. RESULTS: One hundred nine subjects completed the 6-week trial; 15 patients (41%) receiving methylphenidate and 12 patients (36%) receiving pemoline demonstrated clinically significant improvement compared with 6 patients (15%) receiving placebo. Patients receiving methylphenidate or pemoline demonstrated significantly more improvement in fatigue on several self-reported rating scales (PFS total score, P=.04; affective subscale, P=.008; sensory subscale, P=.04; and VAS-F energy subscale, P=.02). Analysis of the regression slopes by means of hierarchical linear modeling demonstrated a significantly greater rate of improvement in PFS total scores among patients receiving psychostimulants compared with the placebo group (P=.02). There were no significant differences in the efficacy between methlyphenidate and pemoline on any outcome measure studied. Improvement in fatigue was also significantly correlated with improvement in measures of depression, psychological distress, and overall quality of life. Severe side effects were relatively uncommon among this sample, and only hyperactivity or jitteriness occurred significantly more often among subjects receiving active medication. CONCLUSIONS: Many patients with HIV- and acquired immunodeficiency syndrome-unrelated fatigue respond favorably to treatment with methylphenidate or pemoline. Both psychostimulants appear to be equally effective and significantly superior to placebo in decreasing fatigue severity with minimal side effects. Moreover, improvement of fatigue was significantly associated with improved quality of life and decreased levels of depression and psychological distress.

Ambulatory Care↗

Paan without tobacco: an independent risk factor for oral cancer.

Oral cancer is the second most common cancer in women and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of piper betel leaf that contains areca nut, lime, condiment, sweeteners, and sometimes tobacco, which is also used extensively. We did this study to clarify the independent association of paan and oral cancer. Between July 1996 and March 1998, we recruited biopsy-proven, primary cases of oral squamous-cell carcinoma, from 3 tertiary teaching centers in Karachi, Pakistan, and controls pair-matched for age, gender, hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 cases and 149 controls. Approximately 68% of the cases were men, 49 years old on average, the youngest being 22 years old and the eldest 80. People with oral submucous fibrosis were 19.1 times more likely to develop oral cancer than those without it, after adjusting for other risk factors. People using paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as compared with non-users, after adjustment for other covariates. This study identifies an independent effect of paan without tobacco in the causation of oral cancer. Its findings may be of significance in South Asian communities where paan is used, and among health-care providers who treat persons from South Asia.

Adolescent↗

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Adaptation, Physiological↗