SEXUAL MEDICINE: Sexual Selection and Genital Evolution: An Overview

IntroductionGenital morphology (especially male) among the animal kingdom is characterized by extensive differences that even members of closely related species with similar general morphology may have remarkably diverse genitalia.AimTo present the sexual medicine specialist with a basic understanding of the current hypotheses on genital evolution with an emphasis on the sexual selection theories.MethodsA review of current literature on the theories of genital evolution.Main Outcome MeasuresAnalysis of the supporting evidence for the sexual selection theories of genital evolution.ResultsSeveral theories have been proposed to explain genital evolution. Currently, the sexual selection theories are being considered to present valid and solid evidence explaining genital evolution. However, other theories, including sexual conflict, are still being investigated. All theories of genital evolution have their own weaknesses and strengths.ConclusionsGiven that many complex biological mechanisms, mostly unknown yet, are involved in the process of genital evolution, it is thus reasonable to conclude that not one theory can independently explain genital evolution. It is likely that these mechanisms may prove to have synergistic rather than exclusive effects. Shamloul R, El-Sakka A, and Bella AJ. Sexual selection and genital evolution: An overview.     

Malignant neoplasm of perivascular epithelioid cells of the liver

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.     

IL-15 in human visceral leishmaniasis caused by Leishmania infantum

Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-gamma (IFN-gamma). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-gamma and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-gamma, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.     

Fluorescent non-porous silica nanoparticles for long-term cell monitoring: Cytotoxicity and particle functionality

Inorganic nanoparticles such as silica particles offer many exciting possibilities for biomedical applications. However, the possible toxicity of these particles remains an issue of debate that seriously impedes their full exploitation. In the present work, commercially available fluorescent silica nanoparticles 25, 45 and 75 nm in diameter optimized for cell labelling (C-Spec® particles) are evaluated with regard to their effects on cultured cells using a novel multiparametric setup. The particles show clear concentration and size-dependent effects, where toxicity is caused by the number and total surface area of cell-associated particles. Cell-associated particles generate a short burst of oxidative stress that, next to inducing cell death, affects cell signalling and impedes cell functionality. For cell labelling purposes, 45 nm diameter silica particles were found to be optimally suited and no adverse effects were noticeable at concentrations of 50 μg ml^?1 or below. At this safe concentration, the particles were found to still allow fluorescence tracking of cultured cells over longer time periods. In conclusion, the data shown here provide a suitable concentration of silica particles for fluorescent cell labelling and demonstrate that at safe levels, silica particles remain perfectly suitable for fluorescent cell studies.     

Involvement of the IP3 cascade in the damage to guinea-pig ventricular myocytes induced by cytotoxic T lymphocytes

 We have shown previously that the interaction between cytotoxic T lymphocytes (CTL) and ventricular myocytes, an in vitro model for heart transplant rejection, results in electrophysiological and morphological alterations indicative of overload of the intracellular [Ca²⁺] ([Ca²⁺]_i). Since these deleterious effects cannot be accounted for by increased L-type Ca²⁺ current (I _Ca,L), we hypothesize that [Ca²⁺]_i overload due to Ca²⁺ release from intracellular stores, e.g. sarcoplasmic reticulum (SR), is initiated by CTL-induced activation of the inositol trisphosphate (IP₃) cascade. Patch-clamp and fura-2-fluorescence techniques were utilized to record transmembrane potentials and [Ca²⁺]_i from ventricular myocytes bound to peritoneal exudate CTL (PEL). In ventricular myocyte-PEL conjugates (after 60 min), resting potential was reduced (compared with the nonconjugated state) from –80.9 ± 0.7 to –59.9 ± 2.5 mV, action potential amplitude from 139.5 ± 1.4 to 80.6 ± 1.7 mV and action potential duration to 50% repolarization (APD₅₀) from 797 ± 97 to 52 ± 12 ms. The ratio of fluorescence at 340 and 380 nm (R _340/380) increased from a control value (in nonconjugated myocytes) of 0.71 ± 0.02 to 2.07 ± 0.03, 30 min after conjugate formation, and exceeded 4.0 at 60 min, before myocyte destruction. Heparin (50 μg/ml), an antagonist of IP₃-induced Ca²⁺ release from SR channels, or U-73122 (2 μM), a phospholipase C (PLC) inhibitor (drugs were included in the pipette solution), prevented PEL-induced morphological and electrophysiological alterations. Accordingly, heparin attenuated the PEL-induced increase in [Ca²⁺]_i; after 60 min of PEL-myocyte interaction, R _340/380 was 1.15 ± 0.09 (compared with approximately 4.0 in the absence of heparin). The results indicate that CTL-mediated damage to ventricular myocytes is, at least partially, mediated by PLC activation and IP₃-induced Ca²⁺ release from intracellular stores. Pharmacological targeting of IP₃ in heart transplant rejection is thus suggested. Received: 3 July 1996 / Received after revision: 21 October 1996 / Accepted: 3 December 1996     

Factors affecting the diagnostic delay in amyotrophic lateral sclerosis

Background

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy).

Objective

To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it.

Methods

We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007.

Results

The median time from onset to diagnosis was 11 months (range: 6–21) for the whole ALS cohort, 10 months (range: 6–15) in bulbar-onset (n = 65) and 12 months (range: 7–23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75–24.25] vs ALS, n = 179, median delay, 9 months [6–15.25], p < 0.001).

Conclusions

The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis.     

Biopsy and the diagnostic evaluation of musculoskeletal tumours: critical but often missed in the 21st century

Bone and soft‐tissue sarcomas are rare and heterogeneous malignancies arising from tissues of mesenchymal origin. Treatment planning is informed by accurate diagnosis for which biopsy is the diagnostic standard. Biopsy in the setting of suspected malignancy is a technically challenging procedure that should only be performed at specialist institutions. Without the requisite expertise, they can compromise the viability of reconstructive procedures and may make necessary amputation to achieve adequate surgical margins. The risk of complications arising from the procedure must be minimized and therefore biopsy should always be preceded by imaging. There must be no attempt at biopsy or excision prior to referral if there is any suspicion of malignancy. Patients with suspected bone and soft‐tissue tumours are best evaluated and treated at specialist sarcoma centres under the care of expert multidisciplinary teams. Prompt referral to a specialist sarcoma centre should always be made prior to biopsy for any suspicious mass that is painful, progressively increasing in size, greater than 5 cm in diameter, deep to deep fascia or recurs following inadvertent excision.