Noncitrus alkaline fruit: a dietary alternative for the treatment of hypocitraturic stone formers

Background and Purpose: Fruits and vegetables are natural suppliers of potassium, bicarbonate, or bicarbonate precursors such as citrate, malate and others-hence, possessing potential effects on citraturia. We aimed to compare the acute effects of a noncitrus (melon) fruit vs citric ones (orange and lime) on citraturia and other lithogenic parameters. Patients and Methods: Two-hour urine samples were collected from 30 hypocitraturic stone-forming patients after an overnight fast and 2, 4, and 6 hours after the consumption of 385?mL (13 oz) of either freshly squeezed orange juice (n=10), freshly blended melon juice (n=10), or freshly squeezed lime juice (n=10). Urinary citrate, potassium, pH, and other lithogenic parameters were determined and net gastrointestinal alkali absorption (NGIA) was calculated. Potential renal acid load (PRAL) and pH from juices were determined. Results: Significant and comparable increases of mean urinary citrate were observed in all groups, whereas mean urinary potassium, pH, and NGIA were significantly increased only after consumption of melon and orange juices. The pH of melon juice was higher and the PRAL value was more negative compared with orange juice, indicating a higher alkalinity. Conclusions: These findings suggested that melon, a noncitrus source of potassium, citrate, and malate, yielded an increase in urinary citrate excretion equivalent to that provided by orange, and hence represents another dietary alternative for the treatment of hypocitraturic stone-formers. Despite its low potassium content, lime also produced comparable increases in citraturia possibly because of its high citric acid content.     

Characterization of a technique for rapid pharmacokinetic studies of multiple co-eluting compounds by LC/MS/MS

A method for rapid pharmacokinetic screening of multiple potential drug candidates has been developed. This technique, based on the ability of liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) to independently monitor multiple components, enables the quantification of substances which may or may not be chromatographically resolved. Our results indicate that the limit of quantitation and accuracy of this multiple-compound LC/MS/MRM quantitation method are comparable to a single-compound LC/MS/MRM quantitation method. No apparent ion suppression due to the existence of extraneous compounds in the analytical solution and biological matrix effect are observed in the range of the calibration curve. The issue of potential residual molecule cross-talk interference existing in the multiple-reaction monitoring mode has been discussed. This multiple-compound LC/MS/MRM quantitation method can be used for high throughput pharmacokinetic screening and to assay mixtures that have co-eluting analytes or similar m/z of precursor/product ion pairs.     

Conservative antibiotic treatment for acute uncomplicated appendicitis is feasible

Purpose

Appendectomy versus conservative antibiotic treatment (CAT) for children with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns regarding the practicality of CAT. We analyzed our center’s experience with CAT for AUA, using a protocol with strict inclusion, exclusion and treatment criteria.

Methods

Non-randomized, prospective cohort study included all children admitted betwee 2014 and 2016, with clinical and laboratory tests suspicious for AUA. Data collected included clinical signs and symptoms; laboratory, ultrasound and pathology results. Follow-up was conducted through clinic visits, telephone conversations and national registry analysis.

Results

Included in CAT: 362 children, 19 underwent appendectomy within 1–2 days. Overall, 75 were readmitted for recurrent acute appendicitis during 22 months (6–43) follow-up. Thirty were treated successfully with antibiotics a second time. The remaining 45 had appendectomy. Overall, 86.8% underwent CAT with no surgery. Histology of all recurrent AUA revealed no perforations.

Conclusion

We confirm the feasibility of conservative management of AUA in children. A rigorous diagnostic plan with strict inclusion and exclusion criteria will lead to high success rate of CAT with a strong safety profile. CAT does not compete with surgery or render appendectomy unnecessary. It is a safe alternative to surgery in selected cases.

     

Carotid bodies and ventilatory response to hypoxia in aminophylline-treated piglets

Peripheral chemoreceptors may be immature in neonatal animals, exhibiting maturational changes in the perinatal period. Even though methylxanthines are respiratory stimulants, many premature neonates do not respond to them. Thus, we hypothesized that carotid body activity is necessary for aminophylline to reverse hypoxia-induced respiratory depression. We exposed 16 anesthetized newborn piglets (age 2-7 days) to hypoxia (inhalation of 12% oxygen) for 5 min. Aminophylline (15 mg/kg iv) was administered either prior to (11 piglets) or following (5 piglets) carotid body denervation (CBD). Before CBD, hypoxia elicited transient initial increases in tidal volume (from 79 ± 4 to 99 ± 1% of maximum, mean ± SE), minute ventilation (from 64 ± 5 to 93 ± 4%), and peak phrenic electroneurogram (from 63 ± 8 to 91 ± 6%, all P < 0.05). This was followed by a decrease in tidal volume, minute ventilation and phrenic electroneurogram (all P < 0.05). Prior to CBD, aminophylline pretreatment prevented the decrease in all the measures of respiratory output during late hypoxia. After CBD, hypoxia induced an initial and sustained depression of ventilation (tidal volume from 100 to 33 ± 14%; frequency from 94 ± 4 to 42 ± 17%; minute ventilation from 100 to 32 ± 14%, all P < 0.05)and phrenic electroneurogram (peak phrenic from 100 to 47 ± 18%; minute phrenic from 85 ± 6 to 55 ± 21%, both P < 0.05). Administration of aminophylline after CBD did not prevent the profound respiratory depression elicited by hypoxia in the chemodenervated piglets. We conclude that aminophylline prevents respiratory depression during late hypoxia, however, in the absence of afferent input generated by the carotid bodies, aminophylline does not reverse respiratory depression induced by hypoxia in anesthetized newborn piglets. Pediatr Pulmonol. 1995; 20:94–100 . © 1995 Wiley-Liss, Inc.     

A Newly Identified Deletion of 970 bp at the α-Globin Locus That Removes the Promoter Region of the α1 Gene

The most common causes of α-thalassemia (thal) are deletions that remove a part, or one or both of the functional α-globin genes. These deletions cause diminished expression of the α-globin protein, which may result in relatively low hemoglobin (Hb) and/or mean corpuscular volume (MCV) values. We here report the identification of a 970 bp deletion in the α1-globin gene that encompasses the entire promoter region of the α1-globin gene and 26 bp encoding the 5′ end of the mRNA. Thus, the affected α1-globin gene is prone to be nonfunctional. We therefore nominated the newly identified deletion allele α?α^Δ970. The MCV values of four related carriers of the α?α^Δ970 allele were slightly lowered, consistent with the presence of three functional α-globin genes.     

The effect of organochlorine insecticides on serum cholesterol level in people occupationally exposed

Bulletin of Environmental Contamination and Toxicology - Serum cholesterol was determined in 206 workers occupationally exposed to organochlorine insecticides (OCI) and in 86 workers...     

A signaling pathway by a new synthetic lipid A analog,ONO-4007, in RAW264.7 cells

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. We have reported that ONO-4007 could be a new bio-logical response modifier for the treatment of tumor necrosis factor (TNF)-alpha-sensitive tumors. In this study, we confirmed that ONO-4007 activated a murine macrophage cell line, RAW264.7, and that the activated RAW264.7 cells produced TNF-alpha. RAW264.7 cells stimulated for less than 15 min with ONO-4007 (40 g/ml) did not produce TNF-alpha (less than 4 U/ml). However, 24 h stimulation with ONO-4007 induced TNF-alpha production (more than 256 U/ml) in RAW264.7 cells. Although P38 in mitogen-activated protein kinase of the RAW264.7 cells was not tyrosine phosphorylated by ONO-4007 stimulation, ERK1 of the RAW264.7 cells was tyrosine phosphorylated for 5-15 min by ONO-4007 stimulation. Tyrosine phosphorylation of ERK1 decreased gradually from 15 min after stimulation and almost disappeared 60 min after stimulation. These findings indicate that ONO-4007 stimulates RAW264.7 cells immediately and induces tyrosine phosphorylation of ERK1 in the RAW264.7 cells for 5-15 min. These data suggest that the signal transduction pathway of ONO-4007 may be similar to that of lipopolysaccharide.     

The antidepressant activity of Hypericum perforatum L. measured by two experimental methods on mice

The pharmacological approach to the treatment of depression includes a long-term employment of antidepressants, either in the form of monotherapy or as a combination of several antidepressants with various mechanisms of action. Hypericum perforatum L. (St. John's wort) is the only natural antidepressant. Several constituents of the extract, such as hypericin and hyperforin, seem to be important for this effect. H. perforatum is considered to be an effective alternative to other therapeutic agents in the treatment of mild to moderate depression. The paper describes the investigation of the antidepressant effect of H. perforatum (doses 7, 35 and 70 mg kg(-1) b. m.) on mice using the forced-swimming and tail-suspension methods. As an indicator of the antidepressant effect, it was shown that the immobility time of animals in the forced-swimming and tail-suspension experiments was shorter, i.e. the activity of the animals was higher. With single doses of extract suspension increasing from 7 over 35 to 70 mg kg(-1) the antidepressant effect increased in proportion by 10.1%, 25.8% and 38.6% in the swimming method, and by 12.7%, 16.5% and 24.5% in the tail-suspension method compared to controls. H. perforatum extract displays dose-dependent antidepressant effect at a dose as low as 7 mg kg(-1). Both models have proved to be equally valuable for demonstration of substances with a potential antidepressant effect.