Gut production of GABA by a probiotic formula: an in vitro study.

The objective of this study was to evaluate the influence of a probiotic formula on the production of neuroactive compounds in different parts of the colon in batch culture and in vitro gut simulator experiments. Thirteen lactic acid bacterial strains, belonging to the species Levilactobacillus brevis, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Ligilactobacillus salivarius, Streptococcus thermophilus, were characterised for their in vitro ability to produce neurotransmitters. L. brevis P30021 and L. plantarum P30025 were selected based on their capability to produce γ-aminobutyric acid (GABA) and acetylcholine in vitro. A probiotic formulation with potential psychobiotic activity was prepared and tested in a batch culture of human microbiota monitoring the formation of GABA and acetylcholine. Samples of the three colonic tracts were taken from the Simulator of the Human Intestinal Microbiota (SHIME®) evaluating the production of GABA and other neurotransmitters by LC-MS. Short chain fatty acids (SCFA) by GC and microbiota composition by 16S rRNA gene sequencing were also determined. Probiotic supplementation led to the formation of GABA and acetylcholine with a decrease in glutamate concentrations in the in vitro batch fermentation. Production of GABA after the treatment with probiotics was confirmed in the SHIME® short-term experiment. No differences in short-chain fatty acids were observed up to 72 h of fermentation. Different microbiota composition was found in the three different parts of the colon, with a higher abundance of Veillonellaceae in the ascending colon vessels. The probiotic-exposed microbiota showed higher levels of Bacteroides, a gut microbe associated with anti-inflammatory activities and a potential GABA producer. Results demonstrate the impact of the tested probiotic formula on gut microbiota structure and GABA production. In conclusion, the probiotic treatment changed the microbiota composition and increased neuroactive metabolites production, indicating promising potential as psychobiotics, even if further clinical evidence is needed to confirm the effectiveness of these probiotics in improving mental health.

Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality.

BACKGROUND: Sexual desire is affected by endocrine and psychosocial factors. Menopausal hormonal changes are relevant to the causes of sexual dysfunction during reproductive aging. AIM: To evaluate the effects of different types of hormonal replacement therapy (HRT) on sexual function, frequency of sexual intercourse, and quality of relationship in early postmenopausal women. We recruited 48 healthy postmenopausal women aged 50-60 years (mean age 54.5 ± 3.3 years). Women with climacteric symptoms were uniformly randomized into three groups receiving either dehydroepiandrosterone (DHEA 10 mg) daily, or daily oral estradiol (1 mg) plus dihydrogesterone (5 mg), or daily oral tibolone (2.5 mg) for 12 months. Women who refused hormonal therapy were treated with oral vitamin D (400 IU). Efficacy was evaluated using the McCoy Female Sexuality Questionnaire before treatment and after 12 months. We evaluated the hormonal profile before treatment and after 3, 6 and 12 months. RESULTS: The groups receiving DHEA or HRT reported a significant improvement in sexual function compared to baseline (p < 0.001 and p < 0.01, respectively) using the McCoy total score. The quality of relationship was similar at baseline and after 3, 6 and 12 months of treatment. There were significant increases in the numbers of episodes of sexual intercourse in the previous 4 weeks in women treated with DHEA, HRT and tibolone in comparison with the baseline value (p < 0.01, p < 0.05, p < 0.01, respectively). No changes in the McCoy score occurred in women receiving vitamin D. CONCLUSIONS: Daily oral DHEA therapy at the dose of 10 mg, HRT and tibolone all provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women.

Beam energy recovery for fusion and collector design for tests on compact sources.

The next fusion project DEMO, which will be the evolution of the experimental fusion reactor [International Tokamak Experimental Reactor (ITER)], would require a high efficient energy production. As in ITER, DEMO will use fast Neutral Beam (NB) injectors to increase the plasma temperature needed for the fusion reaction. A way to recover the electric energy production efficiency in DEMO could be the beam energy recovery in the NB production, which is produced by a D- beam, neutralized by a gas cell with 60% efficiency. A compact energy recovery device with an axisymmetric cylindrical ion collector that uses only decelerating electric fields combined with the beam space charge effect has been recently proposed. It can be used for a test on the beam of the NIO1 (Negative Ion Optimization 1) source, a compact ion source (scaled down from ITER size sources) that has been developed at INFN-LNL and Consorzio RFX (Padua). The detailed collector design to be used on one of the beamlets of the NIO1 source within typical space limitation is presented and discussed here. Furthermore, a preliminary trajectory simulation for a beam with a rectangular geometry similar to the beam used in ITER to verify the beam recovery for a nonaxial symmetric geometry is also shown.

Beam and installation improvements of the NIO1 ion source.

The NIO1 (Negative Ion Optimization phase 1) source can provide continuous beam operation, which is convenient for systematic parameter and equipment studies. Even in the pure volume production regime, the source yield was found to depend on conditioning procedures. Magnetic configuration tests continued adding magnets to the existing setup; the filter field component Bx has been progressively extended to span the -12 to 5 mT range, and as a trend, source performances improved with |Bx|. The progress of camera beam diagnostics and of the quality of the volume-produced H- beam is also shown. The status, off-line results, and reliability of a first NIO1 cesium oven are discussed; other upgrades in preparation (cavity ring down spectrometer, the end calorimeter, and conceptual tests of the energy recovery system) are also listed.

Apathy in Parkinson's disease: differences between caregiver's report and self-evaluation.

Apathy is a state of diminished goal-directed speech, motor activity and emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to 62%. Several studies have investigated the relationships between apathy and other dimensions of PD, but little is known about possible discrepancies between self-evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this study is twofold: 1) to investigate the differences in apathy evaluations according to the point of view from which apathy is reported (SE vs CR); 2) to identify the possible relationships between each of the two evaluations (SE and CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES version correlated with depression, whereas both correlated with motor impairment, disease stage and behavioral symptoms. Mini-Mental State Examination and Frontal Assessment Battery scores showed significant negative correlations only with AES-SE scores. Our findings suggest that the point of view from which apathy is seen can lead to significant discrepancies, even when using the same tool. This should be taken into account in order to obtain correct assessment of this disabling and distressing symptom.

[Aging and sexuality in women]. / Invecchiamento e sessualità nelle donne.

A large number of biological, psycho-relational and socio-cultural factors are related to women's sexual health and they may negatively affect the entire sexual response cycle inducing significant changes in sexual desire, arousal, orgasm and satisfaction during the entire reproductive life span. In spite of the high prevalence of sexual problems with increasing age, sexual retirement is not an inevitable consequence of the passage of time and a high proportion of men and women remains sexually active well into later life, a result of changing attitudes toward sexuality and the availability of effective treatments for sexual dysfunction. Population-based studies reported an age-related decline of sexual functioning and an additional adverse effect of menopausal status. Ageing per se interferes with the level of sexual performance, but sexual behaviour of midlife and older women is highly dependent on several factors such as general physical and mental well-being, quality of relationship and life situation. Sex hormones, mainly low levels of estradiol, are relevant for the lack of sexual awareness and vaginal receptivity in naturally menopausal women. Even diminished levels of androgens, as it more frequently occurs in surgically menopausal women, has a negative impact on desire and sexual responsiveness. Several hormonal treatments have been used locally or systemically to alleviate sexual symptoms, especially by using estrogen plus androgen preparations and tibolone, with noticeable results on drive, enjoyment, lubrication, ability to reach orgasm and initiation of sex. However, sexual counseling and individualized management is mandatory to obtain meaningful and long-lasting results in clinical practice.

Placental barrier breakage in preeclampsia: ultrastructural evidence.

OBJECTIVE: It is known that the placenta acts as an immunological barrier between the mother and fetal "graft" allowing two antigenically different organisms to tolerate one another. Preeclampsia may be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy. STUDY DESIGN: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined. RESULTS: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels. CONCLUSIONS: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia.

A perspective on converting enzyme inhibitors and calcium channel antagonists in diabetic renal disease.

Hypertension and renal disease are major causes of morbidity and mortality in the diabetic population, with the presence of microalbuminuria established as a predictor of excess mortality. Numerous attempts, both pharmacologic and nonpharmacologic, have been made to intervene in the disease process. Experimental and clinical evidence suggests that the converting enzyme inhibitors and, more recently, certain calcium antagonists have beneficial effects on renal function above and beyond those simply due to blood pressure control. These effects are likely attributable to favorable systemic and renal hemodynamic changes as well as to direct cellular effects. However, intervention with these agents in various rat models of diabetes or hypertension is initiated very early. Hence, some of the beneficial renal effects may not be as dramatic in clinical practice because of the more commonly advanced stage seen at the time of intervention. We present an overview of the histologic, renal hemodynamic, and antiproteinuric effects of these agents in the experimental setting, as well as the clinical evidence supporting the use of angiotensin-converting enzyme inhibitors and certain classes of calcium antagonists in diabetic renal disease.

The signal-averaged electrocardiogram in cardiac transplantation. A noninvasive marker of acute allograft rejection.

Cardiac allograft rejection represents a major cause of morbidity and mortality in transplanted patients. Noninvasive markers of rejection have been sought, though transvenous endomyocardial biopsy remains the "gold standard" for the diagnosis of rejection. Sixty-one signal-averaged electrocardiograms (five in patients with rejection and 56 in patients without rejection) were obtained on 41 patients and prospectively analyzed in frequency domain via fast Fourier transform (FFT). Patients with acute allograft rejection demonstrate a significant increase in the high-frequency components of the QRS complex upon FFT analysis (QRS area ratio 203 +/- 57 vs. 66 +/- 10, P = 0.0007) compared with patients without rejection. Thus, frequency domain analysis may be a useful noninvasive marker of acute cardiac allograft rejection.

HLA-DR in couples associated with preeclampsia: background and updating by DNA sequencing.

The placenta acts as an immunological barrier between the mother and the fetal "graft", allowing two antigenically different organisms to tolerate one another. In placentae from preeclamptic women, we have demonstrated, by an ultrastructural assessment and an immunohistochemical study, a placental barrier breakage leading to the mixing of maternal and fetal antigenically different blood. This condition could be responsible for the triggering of a maternal rejection reaction that we presume to be at the basis of the preeclamptic syndrome. Thus, we have investigated the Human Leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with preeclampsia, their partners and in control couples using the serological Terasaki tecnique. The results showed a statistically significant increase of HLA-DR homozygosity and a reduced antigenic variety in the preeclamptic women and their partners with respect to controls. In this update, we have examined the 2nd exon of the human gene, HLA-DRB1, on the short arm of the chromosome 6 using DNA sequence-based typing (S-BT) PCR in 56 preeclamptic couples and 64 control couples. The results have confirmed the significant excess of HLA-DR homozygosity in couples associated with preeclampsia versus controls. From our results, it emerges that HLA-DR homozygosity and the reduced antigenic variety seem to be associated to a major risk for preeclampsia, which further appears to be a "couple's disease".

Cardiovascular adaptation to cyclosporine-induced hypertension.

Arterial hypertension is a complication of cyclosporine therapy in heart transplant recipients. We studied cardiovascular adaptation to cyclosporine-induced hypertension by determining haemodynamic and echocardiographic indexes in 25 cardiac transplant recipients matched by mean arterial pressure, age, sex, height and weight to 25 patients with established essential hypertension. Twenty-five normotensive subjects matched by age, sex and body habitus were used as controls. Systemic vascular resistance was 15% higher (P = 0.07) and cardiac and stroke volume indices were 20% and 25% lower (P < 0.01), respectively, in the hypertensive cardiac transplant recipients compared with patients with essential hypertension. Patients with essential hypertension and hypertensive cardiac transplant recipients had greater posterior wall thickness and left ventricular mass index than normotensive subjects (P < 0.01); however, hypertensive cardiac transplant recipients had a greater left ventricular mass (245 +/- 7 vs. 223 +/- 8 g, P < 0.05) than patients with markedly established essential hypertension. Left ventricular ejection fraction was significantly lower in hypertensive cardiac transplant recipients when compared with either normotensives or patients with established essential hypertension. These results indicate that established essential and cardiac transplant hypertension are associated with markedly increased systemic vascular resistance. However, after heart transplantation, hypertension is associated with higher systemic vascular resistance, lower cardiac output, stroke volume and stroke work compared with patients with established essential hypertension at the same level of mean arterial pressure. The cardiac adaptation to cyclosporine-induced hypertension has more severe concentric left ventricular hypertrophy and impaired left ventricular systolic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative radiosurgery of pituitary adenomas.

From 1984-1990, 52 patients with pituitary adenomas had postoperative radiosurgery for incomplete surgical removal or regrowth of the tumor. The atraumatic Greitz-Bergström fixation head device was adopted for the stereotactic procedure and irradiation was performed with a linear accelerator. Because of the variability of the tumor response, a 10-20 Gy single dose was directed at 1-2 targets and radiosurgery repeated if the result was unsatisfactory. The median radiation dose was 30 Gy. No adverse effects occurred. Regression of pretreatment symptoms caused by tumor mass was observed in 67% of patients. GH and PRL activity decreased in 20 patients, was stable in 11 and increased in 2 prolactinomas. CT studies showed disappearance of the tumor in 4 patients and shrinkage in 36. Postoperative radiosurgery is a valuable method of treatment whenever pituitary surgery has been incomplete.

The results of radiosurgical management of 139 single cerebral metastases.

Between March 1984 and June 1993, linac radiosurgery was performed in 139 patients for single brain metastases, using the non-invasive (Greitz-Bergström) head fixation system. This atraumatic system was utilized for subsequent stereotactic CT/NMR staging to obtain strictly comparable neuro-imaging. Thus, tumour response was evaluated precisely and radiosurgery repeated (straight after the diagnostic sitting), as needed. No hospitalization or anaesthesia was necessary. The 25 mm target was the maximum size to avoid the risk of radiation induced reactions. In metastases exceeding this limit single doses were directed at more than one target at the same session. Focusing upon single or multiple targets was facilitated by 3-D stereotactic NMR. The results after one single sitting were compared with those obtained after staged sittings in the same patients. Radiosurgery achieved disappearance or shrinkage of the metastasis with resolution of the oedema and mid-line shift in 86% of the 139 patients treated. In 47% of them, however, the success was the result of repeat radiosurgery and staged sittings. The non-invasive procedure is the keystone to optimize the radiosurgical results.

[Albright's syndrome. Report of a case, complicated by pleural effusion and diabetes]. / La sindrome di Albright. Communicazione di un caso complicato da versamento pleurico e diabete.

A case of Albright's disease in a 54-yr-old man is presented. A brief account of the nosological placement of the disease is followed by a review of the relevant literature, with particular reference to the clinical, anatomo-pathological, and aetiopathogenetic aspects. The salient points of the reported case were: 1) extensive cutaneous hyperpigmentation; 2) polyostotic fibrous dysplasia involving the skull, humeri, femurs, and pelvis; 3) voluminous bilateral costal cysts, with greater extension on the right; 4) right pleural effusion; 5) diabetes; 6) mental under-development; 7) 1/4 balanced translocation.

[Use of a synchronized protocol of cytostatic drugs in the treatment of advanced lung cancer]. / Osservazioni sull'impiego di un protocollo sincronizzato di citostatici nella terapia del cancro polmonare avanzato.

A synchronised programme consisting of VCR, CTX and MTX has been employed in 57 patients suffering fom lung carcinoma. Average survival was 10.6 months and overall tolerance was good. The best indications are intermittent long-term treatment and retreatment of patients with cancer recalcitrant to the same drugs. With the simplification of cell kinetics study techniques, more meaningful results can be expected in the application of this treatment programme.

Historia magistra vitae (Cic. De or. 2.36). The Prime Objective of Radiosurgery in Acoustic Neurinomas.

The central question of stereotaxic radiosurgery in acoustic neurinomas is how to pinpoint its main objective: is it a better alternative to neurosurgery or an option when surgery is unfeasible? This study is a continuation of the article published in 1995 in Acta Neurochirurgica, but benefits from greater experience, more complete analysis and longer supervision of results. The conclusions that can be drawn to date from our own findings and from others in the literature are the following: radiosurgery can be used not only to prevent neurinoma growth and at the same time to preserve the patient's neurological conditions without the risk of complications, but it can also be counted on to provide a cure. However, radiosurgery as an excising device is more insidious than the microsurgical scalpel, since the narrow beam of radiation, directed to a limited target without opening the skull, is invisible. The expression coined by Lars Leksell regarded precisely the innovation he himself conceived in the 'closed skull operation', with reference to its use in cases of acoustic neurinoma as an alternative to traditional surgery. Hence, whatever technique or instruments are involved, it is always a question of interventional neuroradiology or minimally invasive neurosurgery.

Stereotactic radiation therapy in arteriovenous malformations and brain tumors using the Fixster system.

In brain tumours, stereotactic radiation therapy, performed in a single high dose (SHD) or fractionated (FSR), gives better results than conventional methods. In arteriovenous malformations (AVM), radiosurgery is a well-defined alternative to neurosurgery and embolization, if the malformation is not wider than 3 cm. In large AVMs, a successful combined technique of radiosurgery and FSR has been developed. In a series of 110 patients the experience proved that the atraumatic Greitz-Bergström stereotactic system is appropriate.