Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men.

PURPOSE: In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery. METHODS: Hypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies. RESULTS: In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones. CONCLUSIONS: The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.

A unique neuroendocrine cell model derived from the human foetal neural crest.

PURPOSE: Nowadays, no human neuroendocrine cell models derived from the neural crest are available. In this study, we present non-transformed long-term primary Neural Crest Cells (NCCs) isolated from the trunk region of the neural crest at VIII-XII gestational weeks of human foetuses obtained from voluntary legal abortion. METHODS AND RESULTS: In NCC, quantitative real-time RT PCR demonstrated the expression of neural crest specifier genes, such as Snail1, Snail2/SLUG, Sox10, FoxD3, c-Myc, and p75NTR. Moreover, these cell populations expressed stemness markers (such as Nanog and nestin), as well as markers of motility and invasion (TAGLN, MMP9, CXCR4, and CXCR7), and of neuronal/glial differentiation (MAP2, GFAP, SYP, and TAU). Functional analysis demonstrated that these cells not only possessed high migration properties, but most importantly, they expressed markers of sympatho-adrenal lineage, such as ASCL1 and tyrosine hydroxylase (TH). Moreover, the expression of TH increased after the induction with two different protocols of differentiation towards neuronal and sympatho-adrenal phenotypes. Finally, exposure to conditioned culture media from NCC induced a mature phenotype in a neuronal cell model (namely SH-SY5Y), suggesting that NCC may also act like Schwann precursors. CONCLUSION: This unique human cell model provides a solid tool for future studies addressing the bases of human neural crest-derived neuroendocrine tumours.

Clinical relevance of phenotype/genotype correlations in the diagnosis and therapy of pheochromocytomas/paragangliomas.

Pheochromocytomas and paragangliomas are tumors arising from neural crest-derived cells. They can be sympathetic in origin, catecholamine secreting and located in the abdomen or chest, or parasympathetic, generally non-secreting and located in the head and neck region. It is well established that about 35% of them are genetically determined. Germ-line mutations in one of the 10 so far known susceptibility genes is especially suspected when the tumors are diagnosed in young patients, multiple or recurrent or associated with additional lesions typical of syndromic clinical pictures such as von Hippel-Lindau, Multiple Endocrine Neoplasia type 2 or Neurofibromatosis type 1. Tumor genetic profile determines the type and pattern of catecholamine release, the clinical presentation, the risk of malignancy and may influence the choice of the radiotracers used in functional imaging, the type of surgical procedures as well as the type of medical therapy in the treatment of metastatic disease.

Mitochondrial function and content in pheochromocytoma/paraganglioma of succinate dehydrogenase mutation carriers.

To date, the consequences of succinate dehydrogenase (SDH) impairment on overall mitochondrial functions are still obscure. In this study, we evaluated SDH activity and expression and mitochondrial homeostasis in 57 tissue samples of pheochromocytoma (PHEO)/paraganglioma (PGL) obtained from patients genotyped for PHEO/PGL susceptibility genes. The resulted SDH activity and content always decreased in SDH-mutated tumors, in one out of two MAX-mutated patients and in four patients resulted wild type (wt) at genetic screening. All these four wt patients were further screened for large deletions in SDH genes, TMEM127 and MAX and resulted wt but two had somatic SDHD mutations. The RT-PCR in the MAX-mutated sample suggests that the decrease in SDH depends on complex instability and not on a reduced SDHB expression. SDH mutations neither alter citrate synthase (CS) activity nor the content of voltage-dependent anion channel (VDAC) while the expression of the mitochondrial complex IV (cytochrome c oxidase (COX)) was found extremely variable in all (mutated and wt) samples suggesting an impairment of mitochondrial cristae in these tumors. In conclusion, tumors from patients with germ line SDH mutations invariably show decreased enzymatic activity and content, but an SDH impairment may also depend on SDH somatic mutations or, seemingly, on MAX mutations. The impaired SDH activity in the two wt tissues suggests mutations in other still unknown susceptibility genes. Finally, the extreme variability in COX expression levels is yet to be explained and this strongly suggests to evaluate other mitochondrial features to better understand the mitochondrial role in the pathogenesis of these tumors.

Intravitreal bevacizumab therapy for choroidal neovascularization secondary to age-related macular degeneration: 6-month results of an open-label uncontrolled clinical study.

PURPOSE: To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. METHODS: Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. RESULTS: At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 microm (p<0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean BCVA slightly decreased from 20/100(-1) to 20/125(-3) (not significant, p=0.40). Mean CRT was still inferior to baseline (305 microm, p<0.01). Mean lesion GLD was 4186 microm, not different from baseline values (p=0.59), but superior to 3-month mean GLD (p<0.01). Significant visual field defects or endothelial cell losses were not detected at 3 and 6 months. Laboratory testing did not reveal any clinically significant deviations compared to baseline values. CONCLUSIONS: Intravitreal therapy using bevacizumab over 6 months showed stabilization of visual acuity and choroidal neovascularization activity; the safety data were convincing.

Clear corneal incision of 2.75 mm for cataract surgery induces little change of astigmatism in eyes with low preoperative corneal cylinder.

PURPOSE: To assess the early astigmatic effect induced by 2.75 mm clear cornea incisions with different locations for cataract surgery. METHODS: A total of 146 eyes of different patients were studied prospectively. Cataract surgery was performed by three surgeons, two using a temporal approach and one using a superior approach. For both approaches, the site of the 2.75 mm incision was allowed to vary slightly according to the characteristics of the eye and orbit. Computerized videokeratography was used to measure corneal astigmatism before surgery and after 1, 4, and 12 weeks. Corneal astigmatism was recorded as cylinder and axis and it was then converted to 2 power vector. Model based prediction and comparisons were made for the most commonly used corneal incision sites: 12 (both eyes), 2 (left eye), and 8 (right eye) o'clock meridian. RESULTS: After 3 months the differences in corneal astigmatism (JCC 0 ) between the incisions performed at 12 and 2 o'clock were not statistically significant (-0.08, 95% CI: -0.19, -0.02); the differences in JCC 0 between incisions at 12 and 8 o'clock were -0.17 (95% CI: -0.30, -0.05; p<0.01). After 3 months the change in JCC 0 for the patients with 0.5 D with-the-rule preoperatively were -0.32 (95% CI: -0.44, 0.21; p<0.01) for incisions at 12; -0.24 (95% CI: -0.36, 0.13; p<0.01) for incisions at 2; and -0.15 (95% CI: -0.27, -0.03; p<0.05) for incisions at 8. After 3 months the changes of JCC 0 for the patients with -0.5 D against-the-rule pre-operatively were 0.10 (95% CI: 0.04, 0.23) for incision at 12; 0.18 (95% CI: 0.04, 0.32; p<0.05) for incisions at 2; and 0.27 (95% CI: 0.14, 0.40; p<0.01) for incisions at 8 o'clock. The oblique astigmatic vector (JCC 45 ) was very modest in this sample before surgery and underwent minimal and nonsignificant change after it. CONCLUSIONS: This study has shown that a 2.75 mm clear corneal incision causes a small change of corneal cylinder regardless of incision site.

Clear corneal incision of 2.75 mm for cataract surgery induces little change of astigmatism in eyes with low preoperative corneal cylinder.

PURPOSE: To assess the early astigmatic effect induced by 2.75 mm clear cornea incisions with different locations for cataract surgery. METHODS: A total of 146 eyes of different patients were studied prospectively. Cataract surgery was performed by three surgeons, two using a temporal approach and one using a superi-or approach. For both approaches, the site of the 2.75 mm incision was allowed to vary slightly according to the characteristics of the eye and orbit. Computerized videokeratography was used to measure corneal astigmatism before surgery and after 1, 4, and 12 weeks. Corneal astigmatism was recorded as cylinder and axis and it was then converted to 2 power vector. Model based prediction and comparisons were made for the most commonly used corneal incision sites: 12 (both eyes), 2 (left eye), and 8 (right eye) oclock meridian. RESULTS: After 3 months the differences in corneal astigmatism (JCC 0 ) between the incisions performed at 12 and 2 oclock were not statistically significant (-0.08, 95% CI: -0.19, -0.02); the differences in JCC 0 between incisions at 12 and 8 oclock were -0.17 (95% CI: -0.30, -0.05; p<0.01). After 3 months the change in JCC 0 for the patients with 0.5 D with-the-rule preoperatively were -0.32 (95% CI: -0.44, 0.21; p<0.01) for incisions at 12; -0.24 (95% CI: -0.36, 0.13; p<0.01) for incisions at 2; and -0.15 (95% CI: -0.27, -0.03; p<0.05) for incisions at 8. After 3 months the changes of JCC 0 for the patients with -0.5 D against-the-rule pre-operatively were 0.10 (95% CI: 0.04, 0.23) for incision at 12; 0.18 (95% CI: 0.04, 0.32; p<0.05) for incisions at 2; and 0.27 (95% CI: 0.14, 0.40; p<0.01) for incisions at 8 oclock. The oblique astigmatic vector (JCC 45 ) was very modest in this sample before surgery and underwent minimal and nonsignificant change after it. CONCLUSIONS: This study has shown that a 2.75 mm clear corneal incision causes a small change of corneal cylinder regardless of incision site.

The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action.

The mechanism of action of the anti-apoptotic oncogene Bcl-2 is still largely obscure. We have recently shown that the overexpression of Bcl-2 in HeLa cells reduces the Ca2+ concentration in the endoplasmic reticulum ([Ca2+]er) by increasing the passive Ca2+ leak from the organelle. To investigate whether this Ca2+ depletion is part of the mechanism of action of Bcl-2, we mimicked the Bcl-2 effect on [Ca2+]er by different pharmacological and molecular approaches. All conditions that lowered [Ca2+]er protected HeLa cells from ceramide, a Bcl-2-sensitive apoptotic stimulus, while treatments that increased [Ca2+]er had the opposite effect. Surprisingly, ceramide itself caused the release of Ca2+ from the endoplasmic reticulum and thus [Ca2+] increased both in the cytosol and in the mitochondrial matrix, paralleled by marked alterations in mitochondria morphology. The reduction of [Ca2+]er levels, as well as the buffering of cytoplasmic [Ca2+] changes, prevented mitochondrial damage and protected cells from apoptosis. It is therefore concluded that the Bcl-2-dependent reduction of [Ca2+]er is an important component of the anti-apoptotic program controlled by this oncogene.

Recombinant aequorin and green fluorescent protein as valuable tools in the study of cell signalling.

Luminous proteins include primary light producers, such as aequorin, and secondary photoproteins that in some organisms red-shift light emission for better penetration in space. When expressed in heterologous systems, both types of proteins may act as versatile reporters capable of monitoring phenomena as diverse as calcium homoeostasis, protein sorting, gene expression, and so on. The Ca(2+)-sensitive photoprotein aequorin was targeted to defined intracellular locations (organelles, such as mitochondria, endoplasmic reticulum, sarcoplasmic reticulum, Golgi apparatus and nucleus, and cytoplasmic regions, such as the bulk cytosol and the subplasmalemmal rim), and was used to analyse Ca(2+) homoeostasis at the subcellular level. We will discuss this application, reviewing its advantages and disadvantages and the experimental procedure. The applications of green fluorescent protein (GFP) are even broader. Indeed, the ability to molecularly engineer and recombinantly express a strongly fluorescent probe has provided a powerful tool for investigating a wide variety of biological events in live cells (e.g. tracking of endogenous proteins, labelling of intracellular structures, analysing promoter activity etc.). More recently, the demonstration that, using appropriate mutants and/or fusion proteins, GFP fluorescence can become sensitive to physiological parameters or activities (ion concentration, protease activity, etc.) has further expanded its applications and made GFP the favourite probe of cell biologists. We will here present two applications in the field of cell signalling, i.e. the use of GFP chimaeras for studying the recruitment of protein kinase C isoforms and the activity of intracellular proteases.

Anti-ribosomal P protein antibodies detected by immunoblotting in patients with connective tissue diseases: their specificity for SLE and association with IgG anticardiolipin antibodies.

OBJECTIVE: To assess the prevalence and clinical and serological associations of anti-ribosomal P protein antibodies (anti-P antibodies) in patients with connective tissue diseases (CTDs) and investigate the immunobiological nature of autoantibody clustering in which anti-P antibodies play a part. METHODS: IgG anti-P antibodies in the sera of 267 patients with CTDs and 31 healthy subjects were analysed by immunoblotting performed on cytoplasmic extract of Raji cells. 60 patients with systemic lupus erythematosus (SLE), 32 systemic sclerosis, 46 primary Sjögren's syndrome, 16 poly/dermatomyositis, 11 rheumatoid arthritis, 8 undifferentiated CTD, 72 overlap CTD, and 22 primary antiphospholipid syndrome were studied. Anti-P antibodies were affinity purified by elution from nitrocellulose bound antigen and tested by ELISA for their binding activity to cardiolipin. RESULTS: Anti-P antibodies were detected in 16 (6%) patients and in none of the controls: 12/60 SLE (20%) and 4/80 undifferentiated/overlap patients with CTD (5%). A close association of IgG antibodies with P proteins and with cardiolipin was seen in lupus sera (p=0.0009, odds ratio 18.33). Anti-P antibodies from 9 of 12 anti-P lupus serum samples could be affinity purified and none of the affinity purified fractions cross reacted with ELISA plate coated cardiolipin. CONCLUSIONS: Anti-P immunoreactivity is a specific marker of SLE and lupus-like disease and its detection is recommended as a powerful diagnostic tool. Anti-P antibodies are strongly clustered with IgG anticardiolipin antibodies in lupus sera, even if they are independently elicited. This suggests that their cognate autoantigens play a part in a common pathogenetic pathway in SLE.

Correction for age of anticardiolipin antibodies cut-off points.

Immunoglobulin (Ig) isotypes G, M, and A of anticardiolipin antibodies (aCL) are considered markers of antiphospholipid syndrome (APS). They were determined by ELISA in sera of 100 healthy children aged between 6 months and 16 yrs (mean 5.4 yrs +/-3.4 SD) and 100 healthy elderly subjects aged between 65 and 103 yrs (mean 84.2 yrs +/-8.1 SD). The frequency with which they were detected was compared to that in sera of 100 healthy adults aged between 21 and 47 yrs (mean 25.8 yrs +/-5.2 SD) in order to evaluate if adult aCL cut-off levels were fit for pediatric and elderly populations. The cut-off points were calculated adding 2.5 SD to the mean values and, in the adult group, the results were 11.6 GPL, 7.5 MPL, and 23.9 APL for IgG, IgM, and IgA, respectively. In the children, IgG aCL were positive in 26 cases (26%), IgM and IgA aCL in 1 case (1%) respectively. Statistical comparison of these results to those of adults showed a higher significant frequency for children IgG aCL (P = 0.0001) with the major contribution by children aged between 6 months and 5 yrs, and a lower significant frequency for children IgA aCL (P = 0.041). In elderly subjects IgG aCL were positive in 12 cases (12%), IgM aCL in 4 (4%), and IgA aCL in 37 (37%). In a comparison of these values to those of adults, only elderly IgA aCL frequency was significantly higher (P = 0.0001) with the major contribution by the oldest subgroup. In order to avoid false positive results for IgG aCL in children and for IgA aCL in elderly, as well as false negative results for IgA aCL in children, we introduced three new cut-off points: (1) 27.7 GPL for IgG aCL in children; (2) 13.8 APL for IgA aCL in children; and (3) 51.1 APL for IgA aCL in elderly subjects. These data suggest that a correction for age of aCL cut-off levels should be considered to raise specificity and sensitivity for APS in pediatric as well as in elderly populations.

Bilateral juxtafoveolar telangiectasis in monozygotic twins.

PURPOSE: To report the clinical and angiographic features of two monozygotic twins affected by bilateral group 2 idiopathic juxtafoveolar telangiectasis. METHOD: Case reports. RESULTS: Two 64-year-old women, who were identical twins, were suffering from visual loss. One twin had suffered from visual loss for 1 year and had a visual acuity of 20/25 in both eyes, and the other twin had suffered for 2 years and had a visual acuity of 20/30 in both eyes. Fluorescein angiography disclosed similar fundus features. An analogous area of capillary telangiectasis and leakage was observed in the right macula, where no intraretinal pigment was seen; the left macula showed a similar amount of intraretinal pigment associated with tiny right-angle venules and minimal leakage. CONCLUSION: This observation raises the issue of genetic influences in the pathogenesis of this disease.

The kynurenine metabolic pathway in the eye: studies on 3-hydroxykynurenine, a putative cataractogenic compound.

The rabbit lens has an elevated content of 3-hydroxykynurenine (30HKYN) in spite of a very low activity of the enzymes leading to its synthesis. The iris/ciliary body, on the contrary, has very high activity of 30HKYN synthesizing enzymes but a content of 30HKYN lower than that of the lens. These observations suggest that 30HKYN is formed in the iris/ ciliary body, released into the aqueous humor and then taken up into the lens where it may be used for the synthesis of UV filtering products. An excessive accumulation of 30HKYN in the lens has been associated with cataract formation. We found that available selective inhibitors of kynurenine hydroxylase reduced 30HKYN synthesis in both the lens and the iris/ciliary body.

Transpupillary thermotherapy in the management of circumscribed choroidal hemangioma.

PURPOSE: To report a case of circumscribed choroidal hemangioma effectively managed with transpupillary thermotherapy. METHOD: A 53-year-old man affected by extramacular circumscribed choroidal hemangioma had sustained a decline in visual acuity caused by subretinal fluid exudation into the macular area. Multiple attempts at treatment with scatter photocoagulation over the surface of the lesion for several years had been unsuccessful in reducing tumor-related exudation. The patient was examined on referral and underwent a single session of treatment employing transpupillary thermotherapy. The course of the lesion after treatment was documented with fundus photography and ultrasonography. RESULT: Complete atrophy of the choroidal hemangioma with resorption of subretinal fluid was documented over the 6 months after transpupillary thermotherapy, with improvement in visual acuity. CONCLUSION: Transpupillary thermotherapy is an effective alternative to conventional scatter photocoagulation or radiation therapy for precise ablation of circumscribed choroidal hemangioma.

Scleral fixated intraocular lenses: an angiographic study.

PURPOSE: We reviewed the results, complications, and fluorescein angiographic (FA) findings in eyes that had undergone transscleral fixation of posterior chamber intraocular lenses (IOLs). METHODS: Posterior chamber IOL implantation with scleral fixation was performed on 18 patients. Three patients were aphakic, 14 had an intraoperative posterior capsule rupture during cataract surgery, and one was operated on for a retained lens nucleus and dislocated IOL in the vitreous. Follow-up examinations measured visual acuity, intraocular pressure, and IOL decentration and tilting. In 14 patients, iris and retinal FA were performed. RESULTS: No major complications were noted during the procedure. Mean best-corrected visual acuity was 20/70 preoperatively and 20/30 postoperatively after a mean follow-up of 9.8 months. Fourteen patients achieved a visual acuity of 20/40 or better. Macular epiretinal membranes were diagnosed after surgery in five eyes but only one eye showed significant distortion of the fovea (macular pucker). Iris FA revealed no major vascular abnormalities. Fluorescein angiography showed cystoid macular edema in six cases. Light-induced retinal lesions occurred in six eyes. CONCLUSIONS: Transscleral fixation of posterior chamber IOLs provided adequate visual acuity in most patients. Incomplete visual recovery after surgery may be related to the occurrence of macular edema and epiretinal membranes. Light-induced retinal injury was the major irreversible intraoperative complication.

Outcome of fifty-five newborns of antiphospholipid antibody-positive mothers treated with calcium heparin during pregnancy.

OBJECTIVE: The outcome of 55 infants born to 53 antiphospholipid antibody (aPL)-positive mothers treated during pregnancy with calcium heparin is described. METHODS: The clinical state of the children was evaluated immediately after delivery by a clinical examination, and a neonatological check-up was performed no later than 24 hours after birth. Neonates with problems were transferred to the neonatal intensive care unit. After their discharge from hospital the clinical state of the babies was followed by means of interviews with the pediatricians and mothers for a period varying between 1.33 and 5.66 years (mean 2.51 +/- 0.92 SD). RESULTS: The newborns comprised 30 females and 25 males, including 2 sets of twins, delivered between the 25th and 40th weeks of gestation (mean 36.69 +/- 2.91 SD). They had a mean birth weight of 2.828 g +/- 706.50 SD (range 800-4.000) and a mean Apgar score at 5 minutes of 9.60 +/- 0.68 SD (range 7-10). Soon after delivery, 12 children (21.81%) were admitted to the neonatal intensive care unit for periods varying between 2 and 120 days (mean 30.33 +/- 33.40 SD), after which the clinical course was normal. All of these neonates suffered from complications exclusively due to prematurity. Malformations and signs of thrombosis or other aPL-related disorders were not observed in any of the newborns. During the follow-up, none of the diseases suffered by the 55 children differed from those of the normal pediatric population; in particular, aPL-related manifestations were never observed. CONCLUSION: These data indicate the absence of aPL-related problems in the offspring of aPL-positive mothers treated during pregnancy with calcium heparin.

ED2+ macrophages increase selectively myoblast proliferation in muscle cultures.

We have previously shown by coculturing myoblasts and macrophages that myotube formation is strongly increased in vitro by the presence of an acid stable, heat-labile, soluble growth factor(s) secreted by macrophages. In this paper we obtained macrophages from peritoneal washing which also contained limited amounts of other cells such as lymphocytes and mesothelial cells. We here demonstrate that an ED2-positive (ED2+) macrophage subpopulation is responsible for myoblast enhanced proliferation. ED2+ macrophages were separated by a magnetic-activated cell sorter (MACS) using a monoclonal antibody against ED2, a membrane antigen peculiar to macrophages. Both ED2+ macrophages and their conditioned medium increased myotube formation when added to primary muscle cultures. Furthermore we demonstrate that muscle growth induced by macrophages is mainly the consequence of an increased myoblast proliferation by showing the presence of an increased number of MyoD-positive (MyoD+) myonuclei.

Human satellite cell proliferation in vitro is regulated by autocrine secretion of IL-6 stimulated by a soluble factor(s) released by activated monocytes.

We previously showed that macrophages, besides their scavenger role, selectively induce rat myoblast proliferation in vitro by releasing soluble factors. In this paper we demonstrate a relationship between human-activated monocytes and increased human myoblast proliferation due to IL-6 autocrine secretion by satellite cells. Indeed in the supernatants of muscle cultures treated with activated monocyte-conditioned medium we show by means of an ELISA quantitation a higher autocrine secretion of IL-6 associated with increased myoblast proliferation. This suggests that a growth factor(s) secreted by activated monocytes stimulates IL-6 production by myoblasts and then regulates proliferation of satellite cells.