Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch’s bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.     

Tissue factor in antiphospholipid antibody-induced pregnancy loss: a pro-inflammatory molecule

Fetal loss in patients with antiphospholipid antibodies (aPL) has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically complement activation with generation of the anaphylotoxin C5a, is an essential mediator of fetal injury. We have analysed the role of tissue factor (TF) in a mouse model of aPL-induced pregnancy loss. TF is the major cellular activator of the coagulation cascade but also has cell signaling activity. Mice that received aPL-IgG showed strong TF staining throughout the decidua and on embryonic debris. This TF staining was not associated with either fibrin staining or thrombi in deciduas. The absence of fibrin deposition and thrombi suggests that TF-dependent activation of coagulation does not mediate aPL-induced pregnancy loss.We found that either blockade of TF with a monoclonal antibody in wild type mice or a genetic reduction of TF prevented aPL-induced inflammation and pregnancy loss indicated a pathogenic role for TF in aPL-induced pregnancy complications. In response to aPL-generated C5a, neutrophils express TF potentiating inflammation in the deciduas and leading to miscarriages. Importantly, we showed that TF in myeloid cells, but not fetal-derived cells (trophoblasts), was associated with fetal injury, suggesting that the site for pathologic TF expression is neutrophils. We found that TF expression in neutrophils contributes to respiratory burst and subsequent trophoblast injury and pregnancy loss induced by aPL. The identification of TF, acting as an important pro-inflammatory mediator in aPL-induced fetal injury, provides a new target for therapy to prevent pregnancy loss in the aPL syndrome.     

Role of red cell sorbitol as determinant of reduced erythrocyte filtrability in insulin-dependent diabetics

Summary Erythrocyte deformability measured as filtration index is clearly diminished in diabetics, thus possibly contributing to diabetes-associated microvascular complications. Moreover, the erythrocyte sorbitol level in IDD is clearly higher than that of non-diabetics, suggesting an alteration in the polyol pathway as possible determinant of diabetes-associated complications. Following this line of research, intracellular sorbitol as well as glucose, inositol, galactitol, mannitol and 2,3-diphosphoglycerate have been studied in 21 diabetics and in 14 controls matched for age and sex. In addition to confirming the high levels of intraerythrocytic glucose and sorbitol in diabetic subjects, statistically significant correlations have been demonstrated between sorbitol and filtration index, between plasma glucose, intracellular glucose level and glycosylated hemoglobin, suggesting a relationship between metabolic control and hemorheologic alterations in diabetes.     

Lack of alpha-1 integrin alters lesion morphology during pulmonary Mycobacterium tuberculosis infection

The hallmark of Mycobacterium tuberculosis infection is the granuloma, a highly dynamic immune structure that contains the bacilli during chronic infection. Here, we examined if alpha1beta1 integrin is required in the development and maintenance of the granulomatous structure during pulmonary infection using the alpha1 integrin knockout (alpha1-null) mouse. The alpha1beta1 integrin is expressed on activated macrophages and T cells, and interacts with collagen molecules in the extracellular matrix (ECM), and thus may play a role in the granulomatous process. Following pulmonary infection with virulent M. tuberculosis, lungs of alpha1-null infected mice had striking differences in granuloma structure, as well as distinct and markedly thickened alveolar septae. By day 180, there were regions of cell death within granulomatous lesions, characterized by cellular debris in these mice. To determine if this molecule was necessary for T cell trafficking within the lungs, the expression of CD4, CD44 and CD62L was monitored. The number of activated and IFN-gamma-producing CD4(+) T cells increased in the lungs of alpha1-null mice during the chronic phase of infection, although they had decreased concentrations of TNF-alpha and MMP-9. These results suggest that while alpha1beta1 integrin is not required for trafficking or maintenance of T cells in M. tuberculosis infected lungs, it does play a role in granuloma structure and integrity during the chronic phase of infection.     

The Role of Complement in Pregnancy and Fetal Loss

In the United States, between 1 and 3% of women suffer recurrent miscarriages; 50-70% of all conceptions fail. [1,2] Although in the majority of affected women the cause of recurrent miscarriages is unknown, an immune mechanism involving the inappropriate and subsequently injurious recognition of the conceptus by the mother's immune system has been proposed. Murine models have recently been developed that are relevant to this issue. We and others have identified a novel role for complement as an early effector in the pathway leading to pregnancy loss associated with placental inflammation. Indeed, it appears that inhibition of complement activation is an absolute requirement for normal pregnancy, and that in the antiphosphospholid syndrome overwhelming activation of complement triggered by antibodies (Ab) deposited in placenta leads to fetal injury. Identification of complement activation as a mediator of pregnancy loss and definition of the complement components necessary to trigger such injury is likely to lead to a better understanding of its pathogenesis and to new and improved treatments.     

Affective temperament and attachment in adulthood in patients with Bipolar Disorder and Cyclothymia

Objective

To examine attachment and affective temperament in patients who have been diagnosed with Bipolar Disorder and to investigate possible differences in both variables among Bipolar I Disorder (BD-I), Bipolar II Disorder (BD-II), and cyclothymic patients.

Methods

Ninety (45 male and 45 female) outpatients with bipolar or cyclothymic disorder between the ages of 18 and 65 years were recruited consecutively between September 2010 and December 2011 at the Bipolar Disorder Unit of the Psychiatry Day Hospital affiliated with the University General Hospital “A. Gemelli” in Rome, Italy. Patients were assessed using the Structured Clinical Interview for DSM-IV, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, the Temperament Evaluation of Memphis, Pisa, and San Diego—auto-questionnaire version, and the Experiences in Close Relationships (ECR) questionnaire applied by trained interviewers.

Results

The 3 groups of patients differed only on the ECR Anxiety scores with BD-I patients having the highest anxiety levels, followed by the BD-II patients, and the patients with cyclothymic disorder reporting the lowest level of anxiety.

Conclusions

This finding suggests that bipolar disorder (type I, type II) and cyclothymic/dysthymic temperament are more strongly associated with insecure attachment style as compared to the general population.