Purification and characterization of ribosomal proteins L27 and L30 having antimicrobial activity produced by the Lactobacillus salivarius SGL 03.

AIMS: The aim of this study was to investigate the antimicrobial potential of proteins secreted by a new strain of Lactobacillus salivarius. METHODS AND RESULTS: The secretome of L. salivarius SGL 03 strain was analysed by gel-assisted fractionation and MS/MS to identify low-molecular-mass proteins. This strategy allowed us to identify 10 secreted proteins. Then, a combination of heterologous expression and agar well diffusion was used to characterize them as to their antimicrobial activity, mechanisms of action and stability. Our findings indicate that L27 and L30 proteins of the 50S ribosomal subunit have antimicrobial activity against Streptococcus pyogenes, Streptococcus uberis and Enterococcus faecium. In addition, both proteins are bactericidal against S. pyogenes and maintain their antimicrobial activity after different protease treatments, at acidic pH, after heat treatment, and if stored in a refrigerated ambient at least at 4°C. CONCLUSIONS: The overall results demonstrated that the L27 and L30 ribosomal proteins are of interest as new antimicrobial molecules to prevent the growth of S. pyogenes, S. uberis and E. faecium. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide the first insight into the extra-ribosomal activity of L27 and L30 secreted proteins of L. salivarius. This study demonstrated the capacity of L. salivarius SGL 03 to produce antimicrobial molecules and suggested this strain as a promising probiotic candidate.

Accuracy of mammography and echography versus clinical palpation in the assessment of response to primary chemotherapy in breast cancer patients with operable disease.

The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0) submitted to primary chemotherapy. A low relationship was recorded between tumor size assessed clinically and that evaluated by either mammography: Spearman R = 0.38 or echography: R = 0.24, while a greater correlation was found between the tumor dimension obtained by the two imaging techniques (R = 0.62). According to the WHO criteria, the grade of response of breast cancer to primary chemotherapy, showed by mammography and echography, was less marked than the grade of response seen at clinical examination. Residual tumor size assessed clinically depicted a stronger correlation with pathological findings (R = 0.68) than the residual disease assessed by echography (R = 0.29) and mammography (R = 0.33). Post-chemotherapy histology evaluation revealed pathological complete response in three cases (2.1%). Two of these cases were judged as complete responders by clinical palpation but only one was recognized by mammography, and none by echography. Clinical response, but not the response obtained by the two imaging techniques, was a significant predictor for longer disease free survival (p = 0.04). To conclude, physical examination measurements remain the method of choice in evaluating preoperatively the disease response in trials of primary chemotherapy. Prediction of pathological outcome is not improved by echography and mammography.

Gastric tolerability of nimesulide. A double-blind comparison of 2 oral dosage regimens and placebo.

This double-blind parallel-group study aimed to evaluate, by endoscopic examination, the reaction of the gastric mucosa to 7-day oral administration of nimesulide 100 or 200mg twice daily. Placebo was administered as a reference compound. 30 dyspeptic patients, randomly allocated to 1 of the 3 treatment groups, completed the study. On completion of treatment, 1 patient in each nimesulide dosage group and 2 in the control group showed evidence of gastric injury: 1 patient with slight hyperaemic gastropathy at baseline developed superficial ulcerations after treatment with nimesulide 100mg, and 1 patient with a history of gastric ulcer developed a congested corpus mucosa with several erosions and ulcerations after treatment with nimesulide 200mg; in the placebo group, 1 patient developed hyperaemic antropathy and another patient developed several petechiae and microerosions. The incidence of adverse effects was comparable in all groups and treatment was not associated with any significant modification of the considered haematological and haematochemical parameters.

AIDS-like immunologic alterations in clinically unaffected drug users.

Peripheral blood lymphocyte subpopulations (PBLS) and HLA-DR phenotype have been evaluated in 30 IV drug users who were not affected by acquired immune deficiency syndrome (AIDS). A strongly significant reduction in helper/suppressor ratio was found in these subjects as compared to the control population. When the group under study was subdivided according to the presence or absence of signs of lymphadenopathy syndrome (LAS), the apparently unaffected individuals still had significant modifications in PBLS when compared with controls. These modifications were more marked in subjects within the LAS+ subgroup, who also showed a greater DR5 frequency than those belonging to the LAS- subgroup. The authors concluded that AIDS-like laboratory alterations are present in clinically unaffected IV drug users; the possible role of DR5 in conditioning different individual susceptibility is considered.

Acquired factor VIII inhibitor in a non-haemophilic patient: successful treatment with plasma exchange associated with factor VIII concentrate and immunosuppressors.

We report the successful treatment of a 55-year-old man with an acquired factor VIII inhibitor, the appearance of which followed surgery for a carcinoma of the biliary tract. The patient, who had recurrent life-threatening bleeding episodes, was treated with intensive plasmapheresis, factor VIII concentrates, azathioprine and methylprednisolone. Disappearance of the inhibitor was observed after the second series of plasma exchanges. Controls 2 and 3 months after treatment confirmed the complete absence of the inhibitor and normal levels of factor VIII. The crucial role of plasma exchange is considered and discussed.

Controlled clinical investigation of dimetophrine versus midodrine in the management of moderately decreased arterial blood pressure.

An open, controlled study was carried out in 30 in-patients with low arterial pressure syndrome to compare the effectiveness and tolerance of dimetophrine and midodrine in restoring blood pressure to normal levels and relieving symptoms. Patients were allocated at random to receive treatment for 15 days with either 100 mg dimetophrine tablets or 2.5 mg midodrine tablets and dosage was adjusted according to each patient's condition. Blood pressure and heart rate were monitored daily, symptoms were assessed every 8 days, and laboratory tests carried out before and after treatment. The results showed that both drugs significantly increased systolic and diastolic pressure to normal levels during the trial period and no patient failed to respond. Dimetophrine showed a significantly faster onset of action in increasing systolic pressure and levels reached a plateau significantly earlier than with midodrine. No significant differences were observed between the effects of the two drugs on diastolic pressure, although there was a smoother and more progressive increase in dimetophrine-treated patients. Neither drug significantly modified the heart rate. Both drugs were effective in relieving symptoms but, although there was no significant difference between treatments, patients on dimetophrine experienced somewhat faster and greater relief than those receiving midodrine. At the end of the treatment period, only 11% of dimetophrine-treated patients still complained of mild symptoms compared with 33% of those on midodrine. The mean daily dosage was 3.7 tablets of dimetophrine and 4.9 tablets of midodrine. Both drugs were well tolerated; no side-effects were reported and there were no abnormalities in the laboratory tests.