Antisperm antibodies modify plasma membrane functional integrity and inhibit osmosensitive calcium influx in human sperm

BACKGROUND: The hypo-osmotic swelling (HOS) test evaluates the ability of the functional sperm plasma membrane to stretch following cell swelling when exposed to hypo-osmotic solutions. Sperm samples with low HOS scores show low fertilization and pregnancy rates during assisted reproductive techniques, though data are controversial. The aim of this study was to compare the results of the HOS test in a group of normozoospermic men with those in a group of subjects affected by autoimmune infertility due to the presence of antisperm antibodies (ASA) bound to the sperm surface. METHODS: Sperm from normozoospermic and from infertile subjects affected by autoimmune infertility were exposed to hypo-osmolar conditions to verify the effects on intracellular calcium concentrations and acrosome reaction. RESULTS: Sperm samples from infertile men with ASA showed HOS test scores that were significantly lower than those of normozoospermic subjects despite similar sperm viability percentages. Sperm with ASA bound to their plasma membrane showed a reduced rise in intracellular calcium concentrations and acrosome reaction after hypo-osmotic challenge with respect to sperm from normozoospermic subjects without ASA. CONCLUSIONS: Infertile subjects with ASA have a reduced sperm plasma membrane functional integrity that could explain, at least in part, the low fertilization and pregnancy rates observed in these subjects during assisted reproductive procedures. Evaluation for the presence of ASA in all sperm samples showing low HOS test scores in the presence of normal sperm viability percentages is suggested.     

Exercise training improves the IL-10/TNF-α cytokine balance in the gastrocnemius of rats with heart failure

Objective

This study examined the effects of exercise training (ExT) upon concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the gastrocnemius of rats with heart failure (HF) induced by left coronary artery ligation.

Multifocal nivolumab immune-related adverse effects during asymptomatic SARS-CoV-2 infection: causality or casuality?

Neurological Sciences -     

Do antibacterial and antifungal combinations have better activity against clinically relevant fusarium species? in vitro synergism

The aim of this study was to evaluate the susceptibility of 20 clinical isolates of Fusarium spp. to classic antifungals [amphotericin B (AmB), itraconazole (ITR), voriconazole (VRC) and caspofungin (CAS)] and to non-antifungal agents [amiodarone (AMD), doxycycline (DOX) and moxifloxacin (MFX)] by the broth microdilution method. Combinations between these antifungal and non-antifungal agents were also evaluated to determine the fractional inhibitory concentration indices using the chequerboard technique. Synergistic interactions were observed for the following combinations (% synergism): AMD?+?VRC, 80%; MFX?+?AmB, 75%; AMD?+?AmB, 65%; DOX?+?VRC, 60%; MFX?+?VRC, 55%; DOX?+?AmB, 50%; and AMD?+?CAS, 30%. Synergism was not observed for associations with ITR. Antagonism was not seen in any combination. These findings suggest that the combinations of AMD, DOX or MFX with AmB or VRC to have potential for future in vivo investigations.     

14q12 duplication including FOXG1: Is there a common age-dependent epileptic phenotype?

Introduction: Duplications of 14q12 encompassing FOXG1 gene have been recently associated with developmental delay, severe speech impairment, epilepsy, aspecific neuroimaging findings and minor dysmorphisms. Aim and methods: In order to refine the epileptic phenotype associated with 14q12 duplications, we have performed a review of the electroclinical picture of the patients reported to date in the literature, adding a new personal case. A comprehensive set of clinical and instrumental data (with a particular focus on the electroclinical aspects including seizure type, age of onset, EEG at onset and after antiepileptic therapy, drug efficacy) has been taken into account. Results: 9/14 patients carrying 14q12 duplications developed seizures, all in the first months of life. Most of them developed infantile spasms (8/9 epileptic patients) and presented hypsarrhythmia or modified hypsarrhythmia on EEG. After therapy 5/9 patients became seizure free and 3/9 present a good seizure control. At last available follow up, 2/3 of the epileptic patients displayed an almost normal EEG, or a quite organized background activity, with diffuse or focal (mostly temporal) slowing. Conclusions: The review of the available data allowed to recognize a common epileptic core, characterized by early onset, age dependent epileptic encephalopathy with infantile spasms and typical, atypical or modified hypsarrhythmia. Antiepileptic therapy soon led to a good or complete control of seizures with a nearly normal background activity in most patients.     

Role of seminal osmolarity in the reduction of human sperm motility

Mammalian sperm at ejaculation are suspended in the seminal plasma, a heterogeneous mixture deriving from the testicular/epididymal fluid and from secretions of seminal vesicles, prostate and bulbourethral glands. Biochemical characteristics of seminal fluid change along the male reproductive tract when considering its inorganic and organic composition and pH but it is known that in each region of the male genital tract seminal osmolarity is higher than that of serum. It has been previously demonstrated that in invertebrate and vertebrate sperm, seminal plasma osmolarity influences sperm motility and activity, and human sperm have been shown to possess osmosensitive calcium entry pathway that controls important functions such as acrosome reaction and oocyte penetration. In the present study, we have determined seminal plasma osmolarity in a large number of normozoospermic fertile and asthenozoospermic infertile subjects correlating it with sperm motility percentages and kinematic characteristics determined utilizing a computerized motion analysis system. Our results confirm that seminal plasma osmolarity is higher than that of serum (336.1 +/- 20.2 vs. 291.1 +/- 6.9 mOsm/L, respectively). Normozoospermic subjects show seminal osmolarity values that are significantly lower with respect to asthenozoospermic patients (317.8 +/- 12.2 vs. 345.2 +/- 22.6 mOsm/L, p<0.001), irrespective of the cause of asthenozoospermia. Seminal plasma osmolarity negatively correlates with sperm progressive motility percentages and kinetic characteristics (curvilinear velocity, linear velocity, linear coefficient and lateral displacements of sperm head). Furthermore, when sperm from fertile subjects were suspended in medium with an osmolarity increasing from 300 to 600 mOsm, sperm motility percentages and kinetics characteristics were progressively reduced and nearly abolished when medium osmolarity was 600 mOsm. On the contrary, when sperm from asthenozoospermic subjects with high semen osmolarity were resuspended in medium with lower osmolarity, sperm motility parameters improved significantly. Sperm motility parameters did not correlate with seminal plasma concentrations of sodium, potassium, chloride with a weak correlation only with seminal calcium concentration. No correlations are present between seminal plasma osmolarity and ionic composition.In conclusion, the present study confirms and extends the knowledge that, in human, seminal plasma osmolarity is higher than that of serum and demonstrates that seminal osmolarity influences sperm motility characteristics and then it may contribute to the pathogenesis of some forms of asthenozoospermia and male infertility.