pH, healing rate, and symptom relief in patients with GERD

Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.     

Antithrombin V--a rare concomitant symptom in plasmacytoma and autoimmune diseases

Antithrombin V as a pathological inhibitor of coagulation may occur in some rare cases as an accompanying symptom of various basic diseases. In the course of two years, antithrombin V could be identified in 8 patients, with plasmocytoma, lupus erythematodes visceralis, glomerulonephritis or colitis ulcerosa existing as basic diseases. Clinical findings in patients and those gained in analyzing coagulation, procedures of laboratory diagnostics for determining characteristic properties of antithrombin V as well as the therapeutic way of influencing the activity of antithrombin V are represented.     

Health,humanitarian relief,and survival in former Yugoslavia.

Since the World Health Organisation''s effort in former Yugoslavia started in July 1992 it has been concerned with the public health policies of survival. It has provided advice to the United Nations High Commission for refugees, helped the voluntary agencies coordinate their work, assessed health needs, and provided practical help in the field to all parties to the conflict. Three features of the Bosnia war have particularly deplorable effects on health: ethnic cleansing, deliberate attacks on hospitals, and systematic rape. The WHO''s response has included initiatives in nutrition, winter survival, and medical supplies. This experience shows that the WHO can have a useful role complementary to that of other agencies in situations where the basic elements for survival of the population are seriously compromised by war.     

Reduction mammaplasty: a prospective study of symptom relief and alterations of skin sensibility

The aim of the present study was to evaluate the alterations of symptoms and tactile sensibility of the breast after reduction mammaplasty. In a prospective study, 10 women were operated on using the inferior pedicle technique. The patients were examined and interviewed preoperatively and at 2 weeks and 3 and 12 months postoperatively. Tactile sensibility was assessed by Somedic monofilaments applied on nine points on each breast: the nipple, four points on the areola, and in four quadrants of the skin. Preoperative tactile sensibility was compared with tactile sensibility in 10 normal controls. A median of 744 g of tissue was removed. All patients reported relief of shoulder and neck discomfort and improvement of skin sensibility 1 year after the operation. Two weeks after the operation, the sensibility of the areola was reduced (p < 0.05), but the skin sensibility of two quadrants was improved (p < 0.05). The sensibility of the areola was restored to preoperative values during the observation period. At 12 months, sensibility was improved compared with preoperative values both in the upper part of the areola and in three quadrants of the skin (p < 0.05). Significant improvement of skin sensibility was found between 3 and 12 months postoperatively in two quadrants of the breast. Also, the erectile function of the nipple was not altered by the operation. In conclusion, the sensibility of the breast was improved or unchanged 1 year after reduction mammaplasty using the Robbins technique. Continuous improvement of sensibility was found during the 1-year observation period. The evidence provided by this prospective study rules out the common misconception that a reduction mammaplasty gives the patient reduced areola sensibility and altered erectile function.     

Apoptosis induced by picolinic acid-related compounds in HL-60 cells.

We have found that niacin-related compounds, particularly picolinic acid, induced apoptosis in human leukemia cells. In this paper, we investigated whether various picolinic acid-related compounds had apoptosis-inducing activities or not. Particularly, fusaric acid, picolinaldehyde, nicotinaldehyde, 2-aminopyridine, and 3-aminopyridine also induced apoptosis in HL-60 cells. These results suggest that pyridine substituted with various groups and the consequent change of resonance structure may have an important role in the induction of apoptosis.     

Influence of pH, nutrient availability, and growth rate on amine production by Bacteroides fragilis and Clostridium perfringens.

Dimethylamine, methylamine, propylamine, and pyrrolidine were the major amines formed by Bacteroides fragilis NCDO 2217 during the active phase of growth in batch culture. Production of these metabolites was strongly pH dependent and was optimal under acidic conditions (pH 6.0). Low pH also favored the formation of pyrrolidine, cadaverine, and dimethylamine by Clostridium perfringens C523, but the reverse was the case with putrescine, butylamine, and propylamine, where production was maximal at neutral pH. B. fragilis was grown in continuous culture under either starch or casein limitation. Amine formation was influenced by carbohydrate availability and was greatest when the bacteria were grown at high growth rates (dilution rate, 0.20/h) under starch limitation, where they constituted about 18% of the total fermentation products measured. Amine production was optimal and increased concomitantly with growth rate when C. perfringens was grown in glucose-limited continuous culture. Under conditions of high growth rate and glucose limitation, amines accounted for approximately 27% of the fermentation products measured. When glucose in the feed medium was increased from 5 to 15 g/liter, amine production was repressed, and under these nutritional conditions the growth rate had little effect on the process.     

Effects of hypoxia,hypercapnia, and pH on ventilation rate in Nauphoeta cinerea

Injecting 50 μl of a phosphate-buffered Ringer's solution with adjusted oxygen pressure (PO₂), Carbon dioxide pressure (PCO₂) or hydrogen ion concentration (pH) stimulates ventilation in the cockroach, Nauphoeta cinerea. When the pH of the buffered Ringer's is held at 7.08, the observed pH of our cockroach haemolymph, neither a reduced PO₂ nor an elevated PCO₂ produced responses that could account for the observed changes in ventilation in insects during exercise or when exposed to elevated ambient CO₂. Ventilation changes produced by altering the pH of the injected saline are comparable to those observed in active insects and in insects exposed to elevated ambient CO₂. We show that the effect of an elevated ambient CO₂ on ventilation can be accounted for by changes in haemolymph pH.     

The effects of temperature, pH and growth rate on secondary metabolism in Streptomyces thermoviolaceus grown in a chemostat.

Streptomyces thermoviolaceus was grown in a chemostat under conditions of glutamate limitation. The effects of growth rate on production of the antibiotic granaticin, extracellular protein and protease activity as components of secondary metabolism were studied at 37, 45 and 50 degrees C. The amount of each secondary metabolite synthesized was highly dependent on growth rate and temperature. Granaticin yields were highest at growth rates of 0.1 to 0.15 h-1 at 37 degrees C, 0.175 h-1 at 45 degrees C and 0.045 h-1 at 50 degrees C. Protease activity of culture supernatants responded to low nutrient concentration and/or low growth rate. Measurements of extracellular protein revealed complex changes in amount which were dependent on growth rate and temperature. At 45 degrees C and a growth rate of 0.15 h-1, biomass yield was highest between pH 5.5 to 6.5 whereas granaticin synthesis was low at pH 5.5 and rose to highest values at between pH 6.5 and 7.5.     

Melanosomal pH controls rate of melanogenesis, eumelanin/phaeomelanin ratio and melanosome maturation in melanocytes and melanoma cells.

The skin pigment melanin is produced in melanocytes in highly specialized organelles known as melanosomes. Melanosomes are related to the organelles of the endosomal/lysosomal pathway and can have a low internal pH. In the present study we have shown that melanin synthesis in human pigment cell lysates is maximal at pH 6.8. We therefore investigated the role of intramelanosomal pH as a possible control mechanism for melanogenesis. To do this we examined the effect of neutralizing melanosomal pH on tyrosinase activity and melanogenesis in 11 human melanocyte cultures and in 3 melanoma lines. All melanocyte cultures (9 of 9) from Caucasian skin as well as two melanoma cell lines with comparable melanogenic activity showed rapid (within 24 h) increases in melanogenesis in response to neutralization of melanosomal pH. Chemical analysis of total melanin indicated a preferential increase in eumelanin production. Electron microscopy revealed an accumulation of melanin and increased maturation of melanosomes in response to pH neutralization. In summary, our findings show that: (i) near neutral melanosomal pH is optimal for human tyrosinase activity and melanogenesis; (ii) melanin production in Caucasian melanocytes is suppressed by low melanosomal pH; (iii) the ratio of eumelanin/phaeomelanin production and maturation rate of melanosomes can be regulated by melanosomal pH. We conclude that melanosomal pH is an essential factor which regulates multiple stages of melanin production. Furthermore, since we have recently identified that pink locus product (P protein) mediates neutralization of melanosomal pH, we propose that P protein is a key control point for skin pigmentation. We would further propose that the wide variations in both constitutive and facultative skin pigmentation seen in the human population could be associated with the high degree of P-locus polymorphism.     

Intracellular pH controls protein synthesis rate in the sea urchine egg and early embryo.

Direct comparisons between intracellular pH and protein synthesis in the sea urchin egg and early embryo show that pH controls protein synthesis rate in a highly sensitive and reversible manner. The entire increase and maintenance of protein synthesis at fertilization or parthenogenetic activation could be accounted for by a permanent increase in intracellular pH. However, unfertilized eggs whose intracellular pH has been raised artificially by ammonia take at least 30 min longer to reach the rate of protein synthesis seen in fertilized eggs. This time lag for ammonia activation and the decrease in protein synthesis rate during mitosis suggest that other unknown factors can also influence protein synthesis rate during fertilization and early embryogenesis.     

Stomach pH,feeding rhythm and ingestion rate in Oreochromis niloticus L. (Pisces: Cichlidae) in Lake Awasa,Ethiopia

Fish were caught in February and October, 1985 with gill and trawl nets at different time intervals. The length and weight of the fish, the stomach pH and the weight of the stomach contents were determined. The feeding pattern of O. niloticus was observed to have a diel rhythm. The stomach became more acidic towards the afternoon and most of the evening. The pH of the stomach had a significant regression on stomach fullness. The feeding rate of O. niloticus in Lake Awasa was estimated from daily feeding periodicity and rate of gastric evacuation. The fish ingests 11.5% of their wet body weight daily at an average water temperature of 21.5 °C. It is believed that the fish ingests and assimilates adequate supply of energy (9.1 KJ/day) for growth, maintenance and other energy requiring activities of the fish.     

Adipose-derived stem cells applied in skin diseases,wound healing and skin defects: a review

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells.     

Effects of pH on the growth rate, motility and photosynthesis inEuglena gracilis

The influence of pH 3–10 on the growth, motility and photosynthesis inEuglena gracilis was demonstrated during a 7-d cultivation. The cells did not survive at pH<4 and >8, highest growth rate being detected at pH 7. Motility followed a similar patterns as growth rate. Photosynthetic response curves were shown to be of the same type over the whole pH range. High respiration was characteristic for cells grown at pH 5 and 6, the lowest one at 7. At high and also at low pH more active respiration was found which can be considered as a protective response on proton stress. Respiration was not completely inhibited with potassium cyanide. Photosynthesis was the most effective at pH 6; lower and higher pH decreased photosynthetic efficiency. pH affected more the growth rate than the photosynthesis.     

Regulation of the rate of urea synthesis in liver by extracellular pH. A major factor in pH homeostasis in mammals

The views that catabolism of protein leads to net production of acid and that urinary excretion of ammonium ion represents an equimolar excretion of proton are not compatible with basic chemical relationships (Atkinson, D.E., and Camien, M.N. (1982) Curr. Top. Cell. Regul. 21, 261-302). Metabolism of protein produces significant amounts of base (bicarbonate), which is disposed of in the synthesis of urea. In perfused rat liver and in isolated rat hepatocytes, the rate of urea synthesis increases with increase in pH but is not affected by change in the concentration of bicarbonate when pH is held constant. An increase in the concentration of ammonium ion in the suspending medium causes an increase in the rate of urea synthesis by hepatocytes when lactate is the energy source, as previously reported by others, but causes a decrease in the rate of urea synthesis during incubation with glucose or with no added energy source. The rate of urea synthesis decreases when glucose is added to lactate medium. All of these observations are consistent with the view that disposal of bicarbonate is a major function of urea synthesis, and that regulation of the rate of ureagenesis is an important factor in the maintenance of pH homeostasis.