Antimicrobial and genotoxic activities of N-(2-hydroxyethyl)-1,2-benzisothiazol-3(2H)-thione carbamic esters

The antimicrobial properties of N-(2-hydroxyethyl)-1,2-benzisothiazol-3(2H)-thione (1a,b) and its carbamic esters 2a,b-6a,b were tested in vitro against Gram positive and Gram negative bacteria, yeasts and dermatophytes. All compounds markedly inhibit the growth of Gram positive bacteria exhibiting MIC values ranging from 1.25 to 10 micrograms/ml. A strong antifungal activity is exerted against dermatophytes with MICs, in general, between 0.7 and 12 micrograms/ml. Structure-activity relationship studies show that these compounds are, in most cases, more effective than the corresponding benzisothiazolone analogues 7-12. None of the tested compounds shows genotoxic properties by Bacillus subtilis rec-assay and Salmonella-microsome test.     

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation

Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62%), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n=12) and those without (n=22). The two groups were similar in age, sex, Child's stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421±335 vs 183±126; P<0.025), and this was even more evident when rejection occurred (626±375 vs 195±129; P<0.001). Furthermore, during an acute rejection reaction, three cases showed a true steal phenomenon through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.     

Probiotics Administration in Cystic Fibrosis: What Is the Evidence?

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.     

Nonunion fracture healing: Evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model

Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (a) develop a new large animal model for bone atrophic nonunion and (b) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a noncritical, full‐thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM + MSC) for 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas the fracture healing appeared at an early stage in DBM + MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM + MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, whereas MSC do not improve the healing process when cultivated on DBM particles before implantation.     

Greek language processing in naive and skilled readers: Functional properties of the VWFA investigated with ERPs

Neuroimaging studies have provided evidence that the orthographic properties of linguistic stimuli are processed within the visual word form area (VWFA) localised in the left inferotemporal cortex (Cohen & Dehaene, 2004). It is not, however, clear in the literature whether this region responds preferentially to words, distinguishing them from pseudowords, or whether the pseudowords are distinguished from letter-strings on the basis of their orthographic regularity, or again, whether the VWFA distinguishes letters from numbers or from visual stimuli such as chequerboards. Very recently, it has been claimed that there is no evidence that the ill-named VWFA changes its responsiveness during or after reading acquisition (Price & Devlin, 2004). In order to simulate a condition of pre-reading ability in adult readers, we performed this study, in which we compared processing of Greek words and legal pseudowords in mother-tongue Greeks (skilled readers) and monolingual Italian individuals (naive readers) who had no familiarity with the Greek alphabet. ERPs were recorded while volunteers were engaged in a task involving the identification and response to target letters contained within Greek words or pseudowords. The response speed was identical in the two groups (550 vs. 557 ms). ERP data showed that at 165 ms post-stimulus (N1 component) the left lateral-occipital scalp area, probably corresponding to the left ventral occipitotemporal sulcus, discriminates letters of a familiar alphabet, while an unknown alphabet also activates the homologous right-hemispheric region more than 100 ms later. This suggests that the VWFA discriminates nonalphabetic symbols from letter-strings. An analysis of the N2 component showed an increase in the activation of the same region at about 285 ms post-stimulus during the processing of words rather than pseudowords in skilled readers, thus supporting the view that the VWFA discriminates words on the basis of their familiarity. The data seem to suggest that the VWFA is alphabet-specific and that it is based on the shaping of visual area activity during acquisition of the ability to read a given symbolic code.     

Endothelial Dysfunction in Early Systemic Lupus Erythematosus Patients and Controls Without Previous Cardiovascular Events

Objective

To assess the prevalence and risk factors for endothelial dysfunction detected by peripheral artery tonometry in systemic lupus erythematosus patients with early disease without cardiovascular disease and risk factors.

Methods

All the consecutive adult lupus patients, with a disease duration <5 years, seen in our hospital from December 2014 to March 2016 were considered. We excluded patients with any history of cardiovascular disease or risk factors possibly affecting peripheral artery tonometry. Enrolled patients were matched for sex, age, body mass index, and blood pressure with healthy controls with the same exclusion criteria. Patients and controls received a transthoracic Doppler echocardiogram and an evaluation of endothelial function by peripheral artery tonometry.

Results

Twenty patients (100% female) with a median disease duration of 14 months (range 1–58 months), a mean ± SD age of 42 ± 15 years, and a mean ± SD age at diagnosis of 40 ± 16 years were enrolled and matched with 20 controls. Peripheral artery tonometry showed a significantly higher prevalence of endothelial dysfunction (P = 0.003) and vascular stiffness (P = 0.02), while echocardiography detected a significantly higher prevalence of left ventricular concentric remodeling (P = 0.003), grade I diastolic dysfunction (P = 0.047), and subclinical increase of filling pressures (P = 0.039) in lupus patients compared to controls. Among lupus patients, no features were associated with endothelial dysfunction.

Conclusion

A high rate of endothelial dysfunction and vascular stiffness occurs in early lupus patients without cardiovascular risk factors and disease. Larger studies are needed to confirm our results and to look for patients’ characteristics possibly associated with these abnormalities.

     

Osmolality of enteral formula and severity of experimental necrotizing enterocolitis

Purpose

Administration of hyperosmolar formula is regarded as a risk factor for the development of necrotizing enterocolitis (NEC). However, there are limited number of reports about the relationship between formula osmolality and NEC. The aim of this study is to evaluate the effects of formula concentration in an experimental model of NEC.

Methods

We studied experimental NEC in C57BL/6 mice. NEC was induced by giving hypoxia, gavage administration of lipopolysaccharide and gavage formula feeding from postnatal day 5–9. We used two types of formula: (1) hyperosmolar formula (HF): 15 g Similac + 75 ml Esbilac (849 mOsm/kg); (2) diluted formula (DF): dilute hyperosmolar formula with an equal amount of water (325 mOsm/kg). Controls were fed by the mother. On postnatal day 9, the ileum was harvested and evaluated for severity of mucosal injury (hematoxylin/eosin staining) and inflammation (PCR for IL6 and TNFα mRNA expression).

Results

The incidence of NEC was same in both HF and DF (80%). The intestinal inflammatory response was similar between HF and DF (IL6: p = 0.26, TNFα: p = 0.69).

Conclusions

This study indicates the osmolality of enteral formula does not affect incidence of experimental NEC. This experimental study provides new insights into the relationship between formula feeding and NEC.

     

Orchidopexy without ligation of the processus vaginalis is not associated with an increased risk of inguinal hernia

Purpose

To report our experience using a modified orchidopexy with division and non-ligation of the processus vaginalis.

Methods

We performed a single-centre retrospective analysis of all patients who underwent orchidopexy between December 2005 and October 2008 at our institution. In the present technique, the processus vaginalis was gently peeled off the spermatic cord structures as high as possible and severed at the level of the internal inguinal ring without its ligation. Postoperative follow-up was routinely offered to all patients. Additionally, we made a special clinical follow-up, ranging from 1 to 69 months (median 34).

Results

One hundred and twenty-three patients, aged 1–11 years (median 3), underwent 147 orchidopexies during the study period. Of these, 25 were accomplished using conventional division and ligation of the processus vaginalis, and in the remaining 122 orchidopexies, the processus vaginalis was only divided. Of the 137 testes available at follow-up, 134 were in the scrotum and 3 (2 %) required re-do orchidopexy due to secondary reascent, including 2 treated with division only of the processus vaginalis. None of the patients experienced postoperative hydrocele or inguinal hernia development.

Conclusions

Our findings confirm that division without ligation of a patent processus vaginalis is usually followed by spontaneous peritoneal scarring and complete closure of the internal inguinal ring. Present technique is as effective as traditional orchidopexy and saves extra time spent for meticulous closure of the processus vaginalis or peritoneal tears.