Blood cell dynamics in P-selectin-deficient mice

P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin- deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of 51Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury.     

Hyperbaric oxygen as an adjunctive therapy for bilateral compartment syndrome, rhabdomyolysis and acute renal failure after heroin intake

Heroin abuse causes various medical and surgical complications. We report a case of heroin-induced severe bilateral compartment syndrome complicated by rhabdomyolysis, acute renal failure and extremely elevated creatinine kinase. A 30-year-old male heroin addict presented to the emergency department of Mount Vernon Hospital, Mount Vernon, New York complaining of severe pain and burning sensation in both legs and feet 1 day after abusing intravenous heroin. He had severe swelling and tenderness of both legs and feet. Laboratory data revealed tremendous elevation of creatine kinase (236,000 IU/L) consistent with rhabdomyolysis. Acute renal failure developed over subsequent days. Treatment consisted of fasciotomy, hyperbaric oxygen therapy (HBO2) and supportive therapy. The condition gradually improved over 4 weeks and the patient did not require dialysis or amputation.     

Honey increased saliva, plasma, and urine content of total nitrite concentrations in normal individuals

This study investigated effects of oral honey solution on total nitrite, a stable nitric oxide metabolite, in saliva, plasma, and urine samples collected from normal subjects. Fourteen adult healthy volunteers, 25-50 years old, nine males and three females, were enrolled in the study. Total nitrite was estimated in saliva, plasma, and urine after 14 hours of food fasting. Each subject was then asked to drink honey solution (80 g of raw honey dissolved in 250 mL of water). Saliva and blood samples were collected at 1, 2, and 3 hours after ingestion of honey solution for total nitrite assay, while urine samples were collected after 3 hours for total nitrite assay. The mean total fasting nitrite in saliva was 108 +/- 61.3 micromol/L, which was increased to 130 +/- 62.9, 131.2 +/- 59, and 135.1 +/- 64.3 micromol/L at 1, 2, and 3 hours, respectively. Plasma total nitrite was 22.41 +/- 16.22 micromol/L before drinking honey, which was increased to 34.71 +/- 18.13, 29.38 +/- 14.29, and 33 +/- 13.09 micromol/L at 1, 2, and 3 hours, respectively, after drinking honey. Urine total nitrite before drinking honey was 75.8 +/- 54.79 micromol/L, which was increased to 107.8 +/- 70.83 micromol/L 3 hours after ingestion of honey solution. Although not statistically significant, honey solution showed a tendency to increase total nitrite concentration in different biological fluids from humans, including saliva, plasma, and urine.     

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes,urinary volumes and nitrite excretion

OBJECTIVE: To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity. PATIENTS AND METHODS: The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in 'spot' morning urine samples in both the enuretics and normal controls. Enuretics were then given 50 mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment. RESULTS: The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (P<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (P<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in six of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day : night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and 'spot' morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (P>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (P<0.05). CONCLUSION: Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.     

Mixture of honey, beeswax and olive oil inhibits growth of Staphylococcus aureus and Candida albicans

BACKGROUND: Honey, beeswax and olive oil mixture (1:1:1, v/v) is useful in the treatment of diaper dermatitis, psoriasis and eczema. The study was designed to investigate effects of honey, olive oil, and beeswax and the mixture on growth of Staphylococcus aureus and Candida albicans isolated from human specimens. METHODS: The following experiments were performed: 1) honey mixture was poured on holes made on plates seeded with S. aureus or C. albicans, 2) the microorganisms were cultured onto media made of honey mixture alone, nutrient agar-honey mixture and Sabouraud glucose agar-honey mixture. The concentration of honey mixture in nutrient agar or Sabouraud glucose agar was 12.5, 25, 33, 50 and 66% (v/v), and 3) honey, olive oil or beeswax was added onto nutrient agar or Sabouraud glucose agar at a ratio of 1:2 (v/v) and then were seeded with S. aureus or C. albicans. RESULTS: Clear zone of inhibition was observed around holes filled with honey mixture; 3.5 mm on media seeded with C. albicans and 4 mm on media seeded with S. aureus. No growth of either microorganism was obtained on media made of honey mixture alone. The minimum concentration of honey mixture in nutrient agar-honey mixture media required to inhibit S. aureus was 50% and 66% concentration was required to inhibit C. albicans growth onto Sabouraud glucose agar-honey mixture media. No growth of S. aureus or C. albicans was obtained on media containing honey whereas mild to moderate growth was obtained on media containing olive oil or beeswax. CONCLUSIONS: Honey and honey mixture apparently could inhibit growth of S. aureus or C. albicans.     

Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals

Seven men and three women (mean age, 31.2 years; range, 20-45 years) received a strictly controlled regular diet during a 2-week control period, followed by the regular diet supplemented with daily consumption of 1.2 g/kg body weight honey dissolved in 250 ml of water during a 2-week test period. At the end of each period, overnight fasting blood samples were withdrawn for assays of blood glucose, blood minerals, vitamin C, beta-carotene, uric acid, glutathione reductase, immunoglobulin E, hemoglobin, blood indices and cells, serum ferritin, serum iron, and iron-binding capacity. Results showed that honey increased antioxidant agents. It increased blood vitamin C concentration by 47%, beta-carotene by 3%, uric acid by 12%, and glutathione reductase by 7%. Honey increased serum iron by 20% and decreased plasma ferritin by 11%. It increased the percentage of monocytes by 50%, and increased lymphocyte and eosinophil percentages slightly. Honey reduced serum immunoglobulin E by 34% and increased serum copper by 33%. It decreased aspartate transaminase by 22% and alanine transaminase by 18%. Honey markedly reduced lactic acid dehydrogenase by 41%, decreased creatinine kinase by 33%, and reduced fasting blood sugar by 5%. It caused slight elevations in blood zinc and magnesium, hemoglobin, and packed cell volume. It may be concluded that honey increased antioxidant agents, serum iron and blood indices, and trace elements and decreased immunoglobulin E, liver and muscle enzymes, and fasting blood sugar in healthy subjects.