No evidence of family history as a risk factor for herpes zoster in patients with post-herpetic neuralgia.

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell-mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case-control study involving patients affected by post-herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post-herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first-degree relatives [RR 1.03 (CI 95%: 0.78-1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81-1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings.

Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction.

OBJECTIVE: To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. PATIENTS AND METHODS: One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n=82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n=80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. RESULTS: Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. CONCLUSIONS: Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.

Enhanced protein thermostability by Ala-->Aib replacement.

The introduction into peptide chains of alpha-aminoisobutyric acid (Aib) has proven to stabilize the helical structure in short peptides by restricting the available range of polypeptide backbone conformations. In order to evaluate the potential stabilizing effect of Aib at the protein level, we have studied the conformational and stability properties of Aib-containing analogs of the carboxy-terminal subdomain 255-316 of thermolysin. Previous NMR studies have shown that this disulfide-free 62-residue fragment forms a dimer in solution and that the global 3D structure of each monomer (3 alpha-helices encompassing residues 260-274, 281-295, and 301-311) is largely coincident with that of the corresponding region in the X-ray structure of intact thermolysin. The Aib analogs of fragment 255-316 were prepared by a semisynthetic approach in which the natural fragment 255-316 was coupled to synthetic analogs of peptide 303-316 using V8-protease in 50% (v/v) aqueous glycerol [De Filippis, V., and Fontana, A. (1990) Int. J. Pept. Protein Res. 35, 219-227]. The Ala residue in position 304, 309, or 312 of fragment 255-316 was replaced by Aib, leading to the singly substituted fragments Ala304Aib, Ala309Aib, and Ala312Aib. Moreover, fragment Ala304Aib/Ala309Aib with a double Ala-->Aib exchange in positions 304 and 309 was produced. Far- and near-UV circular dichroism measurements demonstrated that both secondary and tertiary structures of the natural fragment 255-316 are fully retained upon Ala-->Aib substitution(s). Thermal unfolding measurements, carried out by recording the ellipticity at 222 nm upon heating, showed that the melting temperatures (Tm) of analogs Ala304Aib and Ala309Aib were 2.2 and 5.4 degrees C higher than that of the Ala-containing natural species (Tm = 63.5 degrees C), respectively, whereas the Tm of the Ala312Aib analog was lowered by -0.6 degree C. The enhanced stability of the Ala304Aib analog can be quantitatively explained on the basis of a reduced backbone entropy of unfolding due to the restriction of the conformational space allowed to Aib in respect to Ala, while the larger stabilization observed for the Ala309Aib analog can be accounted for by both entropic and hydrophobic effects. In fact, whereas Ala304 is a surface residue, Ala309 is shielded from the solvent, and thus the enhanced stability of fragment Ala309Aib is also due to the burial of an additional -CH3 group with respect to the natural fragment. The slightly destabilizing effect of the Ala-->Aib exchange in position 312 appears to derive from unfavorable strain energy effects, since phi and psi values for Ala312 are out of the allowed angles for Aib. Of interest, the simultaneous incorporation of Aib at positions 304 and 309 leads to a significant and additive increase of +8 degrees C in Tm. The results of this study indicate that the rational incorporation of Aib into a polypeptide chain can be a general procedure to significantly stabilize proteins.

Enhanced Protein Thermostability by Ala --> Aib Replacement

The introduction into peptide chains of alpha-aminoisobutyric acid (Aib) has proven to stabilize the helical structure in short peptides by restricting the available range of polypeptide backbone conformations. In order to evaluate the potential stabilizing effect of Aib at the protein level, we have studied the conformational and stability properties of Aib-containing analogs of the carboxy-terminal subdomain 255-316 of thermolysin. Previous NMR studies have shown that this disulfide-free 62-residue fragment forms a dimer in solution and that the global 3D structure of each monomer (3 alpha-helices encompassing residues 260-274, 281-295, and 301-311) is largely coincident with that of the corresponding region in the X-ray structure of intact thermolysin. The Aib analogs of fragment 255-316 were prepared by a semisynthetic approach in which the natural fragment 255-316 was coupled to synthetic analogs of peptide 303-316 using V8-protease in 50% (v/v) aqueous glycerol [De Filippis, V., and Fontana, A. (1990) Int. J. Pept. Protein Res. 35, 219-227]. The Ala residue in position 304, 309, or 312 of fragment 255-316 was replaced by Aib, leading to the singly substituted fragments Ala304Aib, Ala309Aib, and Ala312Aib. Moreover, fragment Ala304Aib/Ala309Aib with a double Ala --> Aib exchange in positions 304 and 309 was produced. Far- and near-UV circular dichroism measurements demonstrated that both secondary and tertiary structures of the natural fragment 255-316 are fully retained upon Ala --> Aib substitution(s). Thermal unfolding measurements, carried out by recording the ellipticity at 222 nm upon heating, showed that the melting temperatures (Tm) of analogs Ala304Aib and Ala309Aib were 2.2 and 5.4 °C higher than that of the Ala-containing natural species (Tm = 63.5 °C), respectively, whereas the Tm of the Ala312Aib analog was lowered by -0.6 °C. The enhanced stability of the Ala304Aib analog can be quantitatively explained on the basis of a reduced backbone entropy of unfolding due to the restriction of the conformational space allowed to Aib in respect to Ala, while the larger stabilization observed for the Ala309Aib analog can be accounted for by both entropic and hydrophobic effects. In fact, whereas Ala304 is a surface residue, Ala309 is shielded from the solvent, and thus the enhanced stability of fragment Ala309Aib is also due to the burial of an additional -CH3 group with respect to the natural fragment. The slightly destabilizing effect of the Ala --> Aib exchange in position 312 appears to derive from unfavorable strain energy effects, since phi and psi values for Ala312 are out of the allowed angles for Aib. Of interest, the simultaneous incorporation of Aib at positions 304 and 309 leads to a significant and additive increase of +8 °C in Tm. The results of this study indicate that the rational incorporation of Aib into a polypeptide chain can be a general procedure to significantly stabilize proteins.

Serum osteocalcin and bone mineral density at various skeletal sites: a study performed with three different assays.

The purposes of this study were threefold: (1) to compare values obtained by three conventional radioimmunoassays for serum bone-gla-protein (BGP) in a population of normal women, (2) to study the relationship between serum BGP and bone mineral density (BMD) measured at four different skeletal sites (lumbar spine, proximal femur, proximal and ultradistal radius), and (3) to compare the results obtained by the three assays with conventional markers of bone turnover. Ninety-seven normal women (age range 25 to 75 years, mean +/- 1 SD = 54.3 +/- 10.9 years) were studied. Three independent assays were used to measure serum osteocalcin levels: a heterologous radioimmunoassay (RIA) (A) (Incstar Co., Stillwater, Minn.), a homologous RIA (B) (Nichols Institute, San Juan Capistrano, Calif.), and a two-site immunoradiometric assay (C) (Cis Biointernational, Gif-sur-Yvette, France). Mean +/- SD values of serum osteocalcin in the group as a whole were 4.05 +/- 1.37 microg/L by assay A, 6.03 +/- 2.90 microg/L by assay B, and 22.67 +/- 7.52 microg/L by assay C. Serum osteocalcin levels increased linearly with age; however, no correlation between serum BGP (whatever the assay used) and age was observed when only postmenopausal women were taken into account. When the effect of age was held constant by means of partial correlation analysis, only serum BGP levels measured by assays B and C were still inversely related with lumbar spine and ultradistal radius BMD; the latter assay was also weakly correlated with Ward's triangle BMD. After all the biochemical and clinical variables taken into consideration were introduced in a multiple regression equation, serum BGP still represented an important predictor of ultradistal radius and lumbar spine BMD only. Regarding relationships with other markers of bone turnover, the assay C in general showed the highest r values. In conclusion, our results indicate that commercially available BGP assays differ analytically and clinically; furthermore for the first time they show the existence of an inverse correlation between serum osteocalcin levels (which reflects bone turnover at the time of examination) and bone mass (which at a given time represents the balance of all previous metabolic events), after the influence of aging is excluded.