Worku Abebe

HERBAL MEDICATION: POTENTIAL FOR ADVERSE INTERACTIONS WITH ANALGESIC DRUGS

The use of herbal supplements in the US has increased dramatically in recent years. These products are not regulated by the Food and Drug Administration (FDA) with the same scrutiny as conventional drugs. Patients who use herbal supplements often do so in conjunction with conventional drugs. This article is a review of potential adverse interactions between some of the commonly used herbal supplements and analgesic drugs. Non‐steroidal anti‐inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (chamomile, motherworth, horse chestnut, fenugreek and red clover) and with tamarind, enhancing the risk of bleeding. Acetaminophen may also interact with ginkgo and possibly with at least some of the above herbs to increase the risk of bleeding. Further, the incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophen when concomitantly used with the potentially hepatotoxic herbs Echinacea and kava, and with herbs containing salicylate (willow, meadowsweet), respectively. The concomitant use of opioid analgesics with the sedative herbal supplements, valerian, kava and chamomile, may lead to increased central nervous system (CNS) depression. The analgesic effect of opioids may also be inhibited by ginseng. It is suggested that health‐care professionals should be more aware of the potential adverse interactions between herbal supplements and analgesic drugs, and take appropriate precautionary measures to avoid their possible occurrences. However, as most of the interaction information available is based on individual case reports, animal studies and in vitro data, further research is needed to confirm and assess the clinical significance of these potential interactions.

Effects of taurine on the reactivity of aortas from diabetic rats.

The effects of the semi-essential amino acid-like nutrient, taurine, on alterations in the reactivities of aortas from male rats with chronic streptozotocin-induced diabetes were examined under in vitro conditions. In the absence of taurine, the contractile responsiveness of endothelium-denuded aortic rings from diabetic rats to norepinephrine, but not KCl, was enhanced compared to controls. This effect of norepinephrine on the diabetic rat aorta appeared to be associated with increased release of intracellular calcium, influx of extracellular calcium and protein kinase C-mediated responses. Incubation of endothelium-denuded aortic rings with 10 mM, but not 5 mM, taurine for 2 h reduced the augmented contractile responses of the tissues from diabetic rats to norepinephrine close to control levels, and this was associated with inhibition of responses linked to the release and influx of calcium, and protein kinase C activation. Endothelium-dependent relaxation of aortas from diabetic rats to acetylcholine was depressed relative to controls. This effect of diabetes was ameliorated close to control levels by incubating the tissues with 10 mM, but not 5 mM, taurine for 2 h. Incubation of nondiabetic rat aortic rings with 45 mM glucose for 3 h caused enhancement of contraction of the vascular smooth muscle to phenylephrine and impairment of endothelium-mediated vasorelaxation to acetylcholine, as compared to control responses. Co-incubation of the tissues with 5-10 mM taurine concentration-dependently reduced the alterations in both contractile and relaxant responses caused by high glucose. Overall, the data suggest that taurine ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for taurines potential as a therapeutic agent for the prevention or amelioration of vascular disorders in diabetes.

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [3H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Renal and glycemic effects of high-dose chromium picolinate in db/db mice: Assessment of DNA damage

This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3] supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower in untreated db/db mice than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100-mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it causes moderate reduction in albuminuria, without affecting the histopathological appearance of the kidney and increasing the risk for DNA damage.

Endothelial dysfunction in diabetes: potential application of circulating markers as advanced diagnostic and prognostic tools

Endothelial dysfunction is a predisposing factor for vascular disease in diabetes, which contributes significantly to the mortality of diabetic patients. The currently utilized assessment methods of endothelial function/dysfunction in humans are associated with various limitations. Circulating endothelial-derived/associated markers have been proposed as potential alternatives for evaluation of the endothelium in condition of vascular disorders. These indicators include von Willebrand factor, soluble thrombomodulin, soluble E-selectin, asymmetric dimethylarginine, tissue plasminogen activator, endothelial microparticles, circulating endothelial cells and circulating endothelial progenitor cells. While tentative evidence is available for most of these biomarkers to serve as reliable sources of information, their usefulness for routine clinical applications has not yet been established. Thus, circulating endothelial markers are currently the subject of intense research interest and it is anticipated that as more information becomes available their improved quantification will provide a suitable diagnostic and prognostic tool for vascular events in diabetes and related diseases.

Herbal supplement use among adult dental patients in a USA dental school clinic: prevalence, patient demographics, and clinical implications

OBJECTIVE This study assessed the frequency and patterns of utilization of herbal supplement products by adult dental patients at a USA dental school clinic. STUDY DESIGN A self-reporting questionnaire was used to collect patient demographics and frequency of herbal supplement utilization along with other information. The questionnaire was distributed and collected at a dental visit. Herbal utilization was related to patient demographics using descriptive analysis. The clinical implications of the findings are discussed. RESULTS Out of 1,240 questionnaires, 1,119 were returned as completed. Of these, 12.6% reported using ≥1 of 21 herbal products. The majority of the users were middle-aged educated caucasian women. Green tea, garlic, echinacea, ginkgo biloba, and ginseng were the top 5 products used. Mostly, supplements were consumed in combination with drugs. CONCLUSIONS The type, prevalence, and frequency of herbal supplement utilization by adult dental patients in this USA dental clinic were generally similar to those reported for other population groups. This observation, coupled with the documented effects of the commonly used herbal products, should alert dental health caregivers to inquire about herbal supplement use when evaluating or treating their patients.

Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats

Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

P1 (Adenosine) Purinoceptor Assays

P1 purinoceptors, or adenosine (ADO) receptors, mediate the biological effects of the endogenous nucleoside, ADO and its analogs. ADO works through four receptor subtypes: A1, A2A, A2B, and A3. Isolated tissue assays used for the pharmacological characterization of ADO receptors based on functional responses are described in this unit. The guinea pig atrium, pig coronary artery, guinea pig aorta ,and mouse aorta have been used for the characterization of ADO receptor subtypes. Curr. Protoc. Pharmacol. 45:4.7.1‐4.7.13.

Endothelial Dysfunction in Diabetes: Role of Circulating Biomarkers as Potential Diagnostic and Prognostic Tools

Diabetes is a major health problem worldwide, type 2 diabetes accounting for about 90% of the diagnosed cases. Vascular disorder is a prominent feature of diabetes and nearly 80% of diabetic mortality is a consequence of this disorder. Endothelial dysfunction is a predisposing factor for vascular disease in diabetes. The methods currently utilized for assessing endothelial function/dysfunction in humans are associated with various limitations making them less applicable for routine tests. Circulating endothelial-linked biomarkers have been proposed to serve as alternative/additional options for evaluating the status of the endothelium in diabetes and related conditions affecting the vasculature. These indicators include von Willebrand factor, thrombomodulin, E-selectin, tissue plasminogen activator, endothelial microparticles, circulating endothelial cells and circulating endothelial progenitor cells. While tentative evidence provides support that most of these biomarkers have the potential to serve as reliable indicators of endothelial status, their usefulness for routine clinical applications has not yet been established. Thus, there is presently intense research interest in circulating endothelial markers and it is anticipated that as more information becomes available, the improved quantification of these substances can provide a more suitable predictive, diagnostic and prognostic means for endothelial-associated events in diabetes and related disorders. The possibility of application of these biomarkers for early detection of endothelial dysfunction can have the added advantage of preventing the vascular complications of diabetes, particularly of type 2 diabetes.