Eli Kassis

Maintaining a Physiological Blood Glucose Level with ‘Glucolevel’, a Combination of Four Anti-Diabetes Plants Used in the Traditional Arab Herbal Medicine

Safety and anti-diabetic effects of Glucolevel, a mixture of dry extract of leaves of the Juglans regia L, Olea europea L, Urtica dioica L and Atriplex halimus L were evaluated using in vivo and in vitro test systems. No sign of toxic effects (using LDH assay) were seen in cultured human fibroblasts treated with increasing concentrations of Glucolevel. Similar observations were seen in vivo studies using rats (LD50: 25 g/kg). Anti-diabetic effects were evidenced by the augmentation of glucose uptake by yeast cells (2-folds higher) and by inhibition of glucose intestinal absorption (∼49%) in a rat gut-segment. Furthermore, treatment with Glucolevel of Streptozotocin-induced diabetic rats for 2–3 weeks showed a significant reduction in glucose levels [above 400 ± 50 mg/dl to 210 ± 22 mg/dl (P < 0.001)] and significantly improved sugar uptake during the glucose tolerance test, compared with positive control. In addition, glucose levels were tested in sixteen human volunteers, with the recent onset of type 2 diabetes mellitus, who received Glucolevel tablets 1 × 3 daily for a period of 4 weeks. Within the first week of Glucolevel consumption, baseline glucose levels were significantly reduced from 290 ± 40 to 210 ± 20 mg/dl. At baseline, a subgroup of eleven of these subjects had glucose levels below 300 mg% and the other subgroup had levels ≥ 300 mg%. Clinically acceptable glucose levels were achieved during the 2–3 weeks of therapy in the former subgroup and during the 4th week of therapy in the latter subgroup. No side effect was reported. In addition, a significant reduction in hemoglobin A1C values (8.2 ± 1.03 to 6.9 ± 0.94) was found in six patients treated with Glucolevel. Results demonstrate safety, tolerability and efficacy of herbal combinations of four plants that seem to act differently but synergistically to regulate glucose-homeostasis.

Long-term clinical, hemodynamic, angiographic, and neurohumoral responses to vasodilation with felodipine in patients with chronic congestive heart failure.

Twenty patients on conventional therapy for severe congestive heart failure (CHF) were randomly assigned to adjunctive treatment with felodipine (n = 10) or placebo (n = 10) and followed over a 6-month period. Baseline clinical, hemodynamic, angiographic, and neu-rohumoral estimates of CHF were comparable in the two treatment groups. These estimates remained virtually unchanged at 6 months in patients on placebo therapy, but circulating noradrenaline levels were further augmented. In patients on felodipine therapy, substantial reductions in left ventricular end-systolic pressure, mean arterial pressure, and systemic vascular resistance were observed at 6 months. This afterload reduction led to a preferential increment in the stroke volume (36%) which increased cardiac output (30%), whereas heart rate tended to decrease. The improved hemodynamics during felodipine treatment were paralleled by marked improvements in the angiographic left ventricular ejection fraction and regional segmental wall motion score. The enhanced contractile state of the left ventricle was accompanied by significant reductions in the augmented plasma levels of catecholamines, and the patient clinical status improved. The 6-month mortality rate in the 20 patients was 40% and indicated a closer relation to baseline noradrenaline plasma levels than to hemodynamic or angiographic estimates of CHF. Despite the limited number of patients, the long-term clinical efficacy of felodipine is thus evidenced in patients with CHF and is related to sustained arteriolar dilatation and improved neurohumoral profile by this vasoselective calcium antagonist.

Sympathetic reflex control of skeletal muscle blood flow in patients with congestive heart failure: evidence for beta-adrenergic circulatory control.

Mechanisms controlling forearm muscle vascular resistance (FMVR) during postural changes were investigated in seven patients with severe congestive heart failure (CHF) and in seven control subjects with unimpaired left ventricular function. Relative brachioradial muscle blood flow was determined by the local 133Xe-washout technique. Unloading of baroreceptors with use of 45 degree upright tilt was comparably obtained in the patients with CHF and control subjects. Control subjects had substantially increased FMVR and heart rate to maintain arterial pressure whereas patients with CHF had decreased FMVR by 51 +/- 11% (mean +/- SEM, p less than .02) and had no increase in heart rate despite a fall in arterial pressure during upright tilt. The autoregulatory and local vasoconstrictor reflex responsiveness during postural changes in forearm vascular pressures were intact in both groups. Further investigations were carried out in the patients with CHF. The left axillary nerve plexus was blocked by local anesthesia in the seven patients. No alterations in forearm vascular pressures were observed. This blockade preserved the local regulation of FMVR but reversed the vasodilator response to upright tilt as FMVR increased by 30 +/- 7% (p less than .02). Blockade of central neural impulses to this limb combined with brachial arterial infusions of phentolamine completely abolished the humoral vasoconstriction in the tilted position. Infusions of propranolol to the contralateral brachial artery that did not affect baseline values of heart rate, arterial pressure, or the local reflex regulation of FMVR reversed the abnormal vasodilator response to upright tilt as FMVR increased by 42 +/- 12% (p less than .02). Despite augmented baseline values, forearm venous but not arterial plasma levels of epinephrine increased in the tilted position, as did arterial rather than venous plasma concentrations of norepinephrine in these patients. The results suggest a beta-adrenergic reflex mechanism elicited by spinal or supraspinal neural impulses and probably modulating a cotransmitter release in the patients with CHF.

Revascularization Compared to Medical Treatment in Patients with Silent vs. Symptomatic Residual Ischemia after Thrombolyzed Myocardial Infarction – The DANAMI Study

Aims: The aim was to compare the effect of revascularization to conservative treatment in patients with residual silent and with residual symptomatic ischemia following acute myocardial infarction (AMI). The study was a subanalysis of the DANAMI (DANish AMI) randomized study of invasive vs. conservative treatment in patients with inducible ischemia after thrombolysis in AMI. Methods and Results: One thousand and eight patients were randomized to invasive or conservative treatment, stratified by the type of ischemia: silent, i.e. ST depression during an exercise test prior to discharge in 56%, or symptomatic, i.e. chest pain occurring either spontaneously during admission or during the exercise test, with or without ST changes, in 44%. Compared to a conservative strategy, invasive treatment reduced the incidence of nonfatal reinfarction, after in median 2.4 years, in both symptomatic patients (13.3–7.2%, p < 0.006) and patients with silent ischemia (10.1 vs. 5.7%, p < 0.05), and of admissions with unstable angina in symptomatic (44.5–27.6%, p < 0.0001) and silent ischemia (21.6–13.3%, p < 0.0006). Conclusions:Compared to conservative strategy, invasive treatment reduces the risk of nonfatal reinfarction and hospital admissions for unstable angina in thrombolyzed post-AMI patients with silent as well as symptomatic exercise-induced ischemia.

Weight Loss in Animals and Humans Treated with 'Weighlevel', a Combination of Four Medicinal Plants Used In Traditional Arabic and Islamic Medicine

Weighlevel, a mixture of extract of four plants used in traditional Arabic and Islamic medicine as well as in European herbal medicine, was prepared and assessed for its safety and efficacy in weight loss. Leaves of Alchemilla vulgaris, Olea europaea and Mentha longifolia L., as well as seeds of Cuminum cyminum, were used. Cultured human fibroblasts treated with Weighlevel did not exhibit any sign of toxicity as evidenced by lactate dehydrogenase release. These results were confirmed in experimental studies on rats where an LD(50) of 15.3 g kg(-1) was observed. Significant antioxidant properties were seen at very low concentrations of Weighlevel (10 μg ml(-1)) as measured by the lipid peroxidation method. Progressive and significant weight loss was observed in chickens given this mixture weekly for 4 weeks compared with controls. Furthermore, a 3-fold increase in the thermogenesis was seen in rat interscapular brown adipose tissue following exposure to different concentrations of Weighlevel extract as determined by measurement of increased oxygen consumption. In addition, a clinical study was carried out among 80 human volunteers with a body mass index (BMI) of 30.67 ± 2.14 kg m(-2). All 80 subjects were asked to continue their usual diet but to eat only three main meals daily and to take one Weighlevel tablet 30 min before each meal. Fourteen subjects were excluded for not following the protocol, and 66 subjects were all evaluated for efficacy and tolerability of Weighlevel monthly for 3 months. Weighlevel was well tolerated by all subjects, and no side effects were reported. A progressive and significant weight loss was seen in these subjects during the whole study period. Higher levels of weight loss were seen in people with BMI of 25-30 kg m(-2) (overweight) compared to people with BMI >30 kg m(-2) (obese). The BMI was reduced after 3 months from 28.5 ± 1.2 and 32.1 ± 1.8 kg m(-2) to 24.5 ± 1.4 and 27.5 ± 2.2 kg m(-2) in overweight and obese group, respectively. Results indicate safety, tolerability and efficacy of Weighlevel.

Complete arterial coronary revascularisation using radial artery conduit for double thoracic artery inlet flow: arterial sling operation

BACKGROUND Coronary artery bypass graft surgery with arterial revascularisation of all diseased coronary vessels is considered highly efficient because arterial grafts have an excellent long-term patency compared with venous grafts. However, problems to reach the infero-lateral wall with the in situ internal thoracic arteries usually require alternative techniques. We present the first results of a new surgical principle using a free radial artery segment to complete the arterial coronary revascularisation and concomitantly connect the internal thoracic arteries. METHODS In patients referred for coronary bypass surgery and three-vessel disease an end-to-end anastomosis of the right internal thoracic artery and the radial artery segment preceded cardiopulmonary bypass, during which side-to-side anastomoses of the radial artery segment were used to revascularise stenotic branches of the right coronary and circumflex arteries. The left internal thoracic artery was used for revascularisation of stenotic branches of the left anterior descending artery, and finally an end-to-side anastomosis of the radial artery segment to the left internal thoracic artery was performed. Coronary artery blood flow was measured in 41 patients with Doppler flow probe. RESULTS One hundred and ninety-two coronary anastomoses (an average of 4.2 per patient) were performed in 46 patients. We measured a mean total blood flow in the arterial sling graft of 104ml/min (range 35-221ml/min), compared with 69 and 68ml/min of the single inlet right and left internal thoracic arteries, respectively (P<0.01). Flow capacities of 104 and 120ml/min of the right and left internal thoracic arteries were measured during clamp of both the aorta and the contralateral internal thoracic artery. The mean crossclamp duration was 77min (range 51-113min). Postoperative angiography demonstrated patent graft anastomoses to all coronary arteries. There were no perioperative deaths or myocardial infarctions. One patient had a minor postoperative stroke. DISCUSSION Complete arterial revascularisation can be achieved by the arterial sling operation with an acceptable crossclamp time and a high early rate of graft patency. The double arterial inlet provides a 50% higher blood flow to the beating heart and two-fold increase in the flow reserve compared with a single inlet. Although further research including long-term follow-up of this new principle is required, the present findings seem promising and suggest that the arterial sling operation has a potential role for complete arterial coronary revascularisation.

Skeletal muscle vascular responses in human limbs to isometric handgrip

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilatation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.

Target vessel revascularization following percutaneous coronary intervention. A 10-year report from the Danish Percutaneous Transluminal Coronary Angioplasty Registry

Objective To present the rate of target vessel revascularization (TVR) in a consecutive and unselected national population over 10 years. Design From 1989 to 1998 all percutaneous coronary interventions (PCIs) performed in Denmark were recorded in the Danish PTCA Registry. Results From 1989 to 1998 the annual rate of PCI rose from 46 to 753 per million inhabitants. From 1995 to 1998 TVR with PCI or coronary artery bypass grafting (CABG) within 9 months from the index PCI decreased significantly (p<0.001) from 21.2% in 1995 (CABG 8.6% vs PCI 12.6%) to 11.7% in 1998 (CABG 4.3% vs PCI 7.4%). Independent predictors for TVR were: coronary stenting (OR 0.60; 95% CI 0.52–0.69, p<0.001), primary success rate (OR 0.69; 95% CI 0.53–0.89, p<0.005), pre-PCI stenosis severity (OR 1.01; 95% CI 1.00–1.01, p=0.03), left anterior descending coronary artery (OR 2.35; 95% CI 1.73–3.19, p<0.001), right coronary artery (OR 1.61; 95% CI 1.17–2.20, p=0.003), sapheneous vein graft (OR 2.03; 95% CI 1.13–3.63, p=0.017) and age (OR 0.99; 95% CI 0.98–1.00, p=0.002). Conclusion Coronary stenting, primary success rate, pre-PCI stenosis severity, age and treated vessel were independent predictors for TVR.

Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction.

Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q-wave myocardial infarction and inducible ischemia (angina pectoris or silent myocardial ischemia) were randomized to a deferred invasive treatment (balloon angioplasty or coronary bypass surgery) or medical treatment. Vital status and non-fatal cardiac events defined as hospitalization caused by acute cardiac events were recorded for a median of 11.4 years. Results. Survival was significantly improved in patients receiving invasive treatment compared to patients treated medically (hazard ratio 0.85 (95% confidence limits 0.73–0.99), p=0.034). Subgroup analysis showed a reduction of non-fatal cardiac events and improved survival among the patients with post-infarction angina pectoris and not among the patients with silent myocardial ischemia. Conclusions. A deferred invasive treatment strategy improves survival compared to medical treatment in patients with inducible myocardial ischemia after a post-thrombolytic Q-wave myocardial infarction.