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Biomedical subjects

A Morabito

Publications and source records attributed to A Morabito.

At least 91 records · Page 5Linked to original sources

A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P = .03). Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P < .001). During a median period of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the 21 untreated controls (sustained response: 33% vs. 0; P < .001). Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P = .01), but not in the untreated group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients.

Adult↗

Enhanced levels of biochemical markers for cobalamin deficiency in totally gastrectomized rats: uncoupling of the enhancement from the severity of spongy vacuolation in spinal cord.

The totally gastrectomized (TGX) rat is a new experimental model for studying the pathogenesis of cobalamin (Cbl)-deficient myelopathy, i.e., subacute combined degeneration, total gastrectomy (TG) serving as a surgical paradigm of human pernicious anemia. We determined the serum levels of some biochemical indicators of Cbl deficiency in TGX rats at 2 to 10 months after TG. Methylmalonic acid (MMA) rose within 2 months and progressively increased thereafter until the end of the investigation period. 2-Methylcitric acid (MCA) rose significantly by 6 months and showed a further increment 4 months later. Homocysteine was only clearly elevated much later than the serum MMA, i.e., 10 months after the operation. The concentrations of MMA, MCA, and cystathionine were increased in kidney, liver, and spinal cord (SC) of TGX rats at 10 months. Chronic treatment of TGX rats with Cbl greatly decreased the serum levels of all the metabolic indicators of Cbl deficiency. Chronic peroral administration of the antibiotic lincomycin to TGX rats in an attempt to suppress the enteric flora markedly decreased serum MMA levels. Only Cbl, however, given either for the first 2 months after TG or for the third and fourth postoperative months (i.e., after SC abnormalities had already appeared) significantly decreased the severity of spongy vacuolation in SC white matter, although not completely preventing or repairing the neuropathological damage. Therefore, neither the early impairment in TGX rats of the Cbl-dependent methylmalonyl-coenzyme A mutase reaction nor the more delayed impairment of the Cbl-dependent methionine synthase step, as reflected by changes in serum metabolite levels, seems to be causally related to the TG-induced spongy vacuolation in SC white matter.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Bone marrow transplantation for chronic myeloid leukemia (CML) from unrelated and sibling donors: single center experience.

This is a report on 60 consecutive patients with chronic myeloid leukemia (CML) who received an allogeneic bone marrow transplant (BMT) in this Unit. Donors were HLA-identical siblings (SIB) (n = 36) or unrelated donors (MUD) (n = 24) matched by serology for HLA A and B and by molecular biology for HLA DR. All patients were prepared with cyclophosphamide 120 mg/kg and fractionated total body irradiation 10-12 Gy. GVHD prophylaxis consisted of cyclosporin A (CsA) starting on day -7 and short-course methotrexate. Bone marrow was unmanipulated in all cases. Cytomegalovirus prophylaxis consisted of acyclovir for SIBs and foscarnet for MUDs. When compared to SIB transplants, MUD patients were younger (29 vs 36 years; P = 0.002), had younger donors (31 vs 39; P = 0.001), had a longer interval between diagnosis and BMT (1459 vs 263 days; P < 0.001) and received a smaller number of nucleated cells at transplant (3.3 vs 4.4 x 10(8)/kg; P = 0.003). More MUDs had advanced disease (50 vs 17%, P = 0.005). The median day to 0.5 x 10(9)/l neutrophils was similar in both groups (18 days for SIBs vs 17 days for MUDs; P = 0.06); the median platelet count on days +30, +50, +100 was significantly (P < 0.01) higher in SIB than in MUD patients (122 vs 38, 113 vs 50 and 97 vs 45 x 10(9)/l, respectively). Acute GVHD was scored as absent-mild, moderate, or severe, in 36, 58 and 6% of SIBs vs 25, 42 and 33% in MUD patients (P = 0.01). Chronic GVHD was comparable (P = 0.1). The actuarial risk of CMV antigenemia at 1 year was 60% in both groups. There were six deaths in SIB patients (two leukemia, two infections, one GVHD, one pneumonitis) and four deaths in MUD patients (three acute GVHD and one infection). Fifty patients survive with a median follow-up of 656 days for SIBs and 485 for MUDs. The actuarial 3-year transplant-related mortality is 12% in SIBs and 17% in MUDs (P = 0.5); the actuarial relapse is 18% in SIBs vs 6% in MUDs (P = 0.4) and 3-year survival 78% in SIBs vs 82% in MUDs (P = 0.7). This study suggests that survival of CML patients after marrow transplantation from unrelated or sibling donors is currently similar, provided the former are well matched. The increased incidence of GVHD in MUD patients is possibly compensated by a lower risk of relapse.

Acyclovir↗

Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80 years old. An echo 2D colour Doppler cooperative study.

In order to find out the normal values and to evaluate the effects of age, heart rate, sex, and haemodynamic and standard echocardiographic parameters on pulmonary venous flow velocity obtained by the transthoracic approach. Doppler pulmonary venous flow parameters were measured in 143 healthy subjects aged from 20 to 80 years. Doppler pulmonary venous flow parameters which had the best correlation with age were: the peak velocity of the systolic wave (r = 0.39) and its integral (r = 0.5), the peak velocity of the diastolic wave (r = -0.6) and its integral (r = -0.44); the systolic (r = 0.68) and diastolic fractions (r = -0.68); the systolic/diastolic peak velocity ratio (r = 0.73) and the systolic/diastolic integral ratio (r = 0.7). The atrial reversal wave did not correlate with age; the atrial reversal wave was more difficult and probably less reliable to measure than the systolic and diastolic waves. The correlations of pulmonary venous flow parameters with mitral flow parameters were also examined. This study showed that, in healthy subjects, despite an increase in the early and atrial waves from the annulus to the tips of the mitral leaflets, there is a similar association between pulmonary venous flow and mitral flow measured at the annulus or at the tips of the mitral leaflets. The intra-observer reproducibility of all the pulmonary venous flow parameters considered were found to be excellent. Moderate inter-observer variability was observed for the systolic, diastolic and atrial reversal wave peak velocities and integrals; however, the systolic/diastolic ratio improved the precision of the measurements. Multivariate analysis showed that age is the principal determinant of the Doppler parameters of pulmonary venous flow: heart rate, sex, body surface area, the size of the left atrium in systole and the left ventricular ejection fraction all influence the Doppler parameters of pulmonary venous flow, even if only slightly.

Adult↗

HLA-A typing: comparison between serology, the amplification refractory mutation system with polymerase chain reaction and sequencing.

In this study we typed HLA-A polymorphisms by a new sequence-based typing (SBT) method, which involved one PCR reaction and four sequencing reactions covering exon 2 and exon 3. This method allowed complete identification of all known HLA-A alleles and revealed the presence of a new allele, named HLA-A*2608. We also introduced sequencing of exon 4 for some samples in order to discriminate the allelic pairs that are identical in exon 2 and 3, thus improving SBT resolution. Finally, we compared the results obtained by SBT with data obtained by serological typing and the amplification refractory mutation system (ARMS-PCR). Together, our results suggest that the SBT here described provides an optimal HLA-A typing technique that may be useful in selecting donor-recipient pairs in bone marrow transplantation between unrelated individuals.

Adult↗

[Intestinal invagination in adults: 3 case reports].

The Authors report their experience in the surgical management of three adults affected by intussusception. The different symptoms and different diagnostic approach, compared to those of childhood, induced the Authors to some evaluations on pathophysiology of intussusception in adults. On the basis of the different pathogenesis some differential criteria between the two forms are stressed, finally suggesting a systematic surgical approach in adults.

Adult↗

The marginal seal of various restorative materials in primary molars.

The use of resin composite restorations in posterior teeth has become an accepted clinical procedure. Microleakage at the posterior composite/tooth interface is a major problem. The in vitro quality of the marginal seal was tested in eighty teeth extracted for orthodontic reasons using a glass-ionomer cement reinforced with amalgam, two light self-curing glass-ionomer cements and a compomer. All the teeth were subjected to thermocycling to simulate clinical situation. Compomers showed the best mechanical and esthetic properties combined with a good marginal seal.

Compomers↗

Mitomycin C, vinblastine, and carboplatin regimen in patients with nonsmall cell lung cancer. A phase II trial.

BACKGROUND: The mitomycin C, vinblastine, and cisplatin (MVP) combination is one of the most frequently used in the palliative setting, but it produces considerable toxicity. Carboplatin and cisplatin have different patterns of toxicity. The goal of this study was to evaluate a combination similar to MVP, using carboplatin instead of cisplatin to render it more feasible in an outpatient setting. METHODS: Inclusion criteria for this study included: inoperable patients or patients relapsing after previous surgery, with nonsmall cell lung carcinoma (NSCLC), a performance status (PS) > 50%, and no previous chemotherapy. The chemotherapy regimen included carboplatin, 300 mg/m2 on Day 1; mitomycin, 8 mg/m2 on Day 1; and vinblastine, 4 mg/m2 on Days 1, 8, and 15 (on Day 15 vinblastine was delivered only in the first cycle) (MVC) every 3 weeks for at least 3 cycles. RESULTS: From August 1991 until August 1994, 70 patients entered the trial. All were evaluable for toxicity and response. The median age was 62 years (range, 40-73 years). The male/female ratio was 60:10 (86%:14%); the ratio of Stage III to Stage IV disease was 26:44 (37%:63%); and the ratio of PS > 70 to < or = 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles] per patient) were delivered, 280 of 296 (95%) in an outpatient setting with only 4 patients requiring hospitalization for treatment delivery. Overall response rate (RR) was 38.6% (95% confidence interval [CI], 27-51%) (1 complete response, 1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months (range, 2-27 months). In Stage III patients the RR was 42% and in Stage IV patients it was 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3 months). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% at 2 years (SE 3.6%). In Stage III patients median survival was 13 months and the 1-year survival rate was 54% (SE 10%); Stage IV patients had a median survival of 7.4 months and a 1-year survival rate of 28% (SE 7%). Delivered dose intensity was: carboplatin, 71%; vinblastine, 60%; and mitomycin C, 77% of the planned dose intensity. The back calculation of carboplatin area under the curve (AUC) with Calvert's formula and with the Cockcroft-Gault glomerular filtration rate estimation, showed a median AUC value of 4 (range, 2-8). Using the more precise Chatelut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of patients, respectively. Grade 2 infection occurred in 10% of patients, with only 1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1 patient; and no case of higher than Grade 1 nephrotoxicity was observed. No pulmonary toxicity was observed. Compliance with treatment was good with only one patient refusal after the first cycle. CONCLUSIONS: Chemotherapy for advanced NSCLS is still controversial, because effectiveness in terms of RR and symptom control must be weighed against treatment toxicity and costs. From our study it appears that MVC is easy to deliver in an outpatient setting, and has good patient compliance, low toxicity profile, and promising RR and response duration. The substitution of carboplatin for cisplatin in regimens for advanced NSCLC should be considered.

Adult↗

Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.

BACKGROUND: The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. METHODS: We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. RESULTS: The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. CONCLUSIONS: Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Adult↗

Abnormal response to exercise in middle-aged NIDDM patients with and without autonomic neuropathy.

The cardiovascular response to exercise in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) patients and the potential role of clinical characteristics and autonomic function were evaluated. One hundred and eight NIDDM patients, aged 40-65 years, were compared with a control group of 112 subjects, matched by age, sex, physical fitness, and presence of hypertension. All subjects performed a maximal exercise test. The diabetic patients completed cardiovascular autonomic neuropathy (CAN) tests: deep breathing, postural hypotension and lying to standing. There were no significant differences in total work capacity, heart rate, and blood pressure, either at rest or at peak exercise between the two groups. Diabetic patients showed significantly lower values of systolic and diastolic blood pressure during exercise, significantly slower recovery of heart rate (at 5th minute the average values were 102.7 +/- 14.1 beats min-1 vs 91.9 +/- 11.1, p < 0.001); and significantly higher proportion of blunted increase of heart rate (9.2% vs 0.9%, p < 0.001) and systolic blood pressure (9.2% vs 0.7%, p < 0.001) during exercise. No correlation between the exercise results and the main clinical characteristic (presence of hypertension, BMI, duration of diabetes, treatment, microalbuminuria, total score of CAN) was observed. These findings suggest that the cardiovascular response to exercise could be impaired also in the absence of signs of CAN. This impairment was higher in patients showing a dysfunction of orthosympathetic activity.

Adult↗

Selecting high-risk early breast cancer patients: what to add to the number of metastatic nodes?

High-risk early breast cancer patients are usually identified by the number of metastatic axillary nodes. To study whether other easily and inexpensively detectable morphological factors are able to detect high-risk patients, we performed a retrospective analysis of tumor size, and skin/fascia and nipple invasion. The data consisted of 941 node-positive cases registered between 1978 and 1991. Tumour size, and skin/fascia and nipple invasion were closely associated with the number of metastatic nodes (chi 2 test). The number of metastatic nodes, tumour size, skin/fascia and nipple invasion significantly affected disease free survival (DFS) and overall survival (OS) at univariate analysis. These results were confirmed by multivariate analysis with a model containing the number of metastatic nodes, tumour diameter categories, skin/fascia invasion, nipple invasion and adjuvant therapy as covariates: all variables significantly and independently affected risk of relapse and of death. All the variables studied were prognostic, within individual nodal categories, for both DFS and OS. In conclusion, the number of metastatic nodes is not the only prognostic tool with which to select high-risk patients for new intensive adjuvant programmes. Tumour size, and skin/fascia invasion or nipple invasion, taken singly or combined, are valuable prognostic factors that can identify patients with few metastatic nodes and poor outcome. On the basis of our data, we believe that a reconsideration of the pT4 category within the pTNM classification is in order, that is, chest wall invasion should be substituted by fascia invasion, and combined skin/fascia invasion could be a subcategory of each class defined by tumour size.

Adult↗

c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases.

PURPOSE: We studied retrospectively the interaction between c-erbB2 overexpression and adjuvant tomoxifen in node-negative breast cancer patients enrolled in the Gruppo Universitario Napoletano 1 (GUN-1) trial. PATIENTS AND METHODS: c-erbB2, evaluated by immunohistochemistry in 145 of 173 patients randomly assigned to 2-year adjuvant tamoxifen or no further therapy, was considered overexpressed if greater than 10% of the cells showed specific membrane staining. The role of each prognostic variable and their independent effect were studied using the Cox model. Disease-free (DFS) and overall (OAS) survival curves were estimated by the Kaplan-Meier method. RESULTS: As of November 30, 1994, the median follow-up period was 12 years. c-erbB2 was overexpressed in 43 of 145 patients (29.7%), which directly correlated with tumor size and inversely with estrogen receptor (ER) level. At univariate analysis, overexpression of c-erbB2 did not affect either DFS or OAS; tamoxifen had a greater effect on reducing the risk of recurrence than of death. Addition of c-erbB2 to a multivariate Cox model that contained menopausal status, tumor size, nuclear grade, and treatment as covariates did not affect the significance of the model for DSF or OAS, whereas addition of the first-order interaction between c-erbB2 and tamoxifen was statistically significant both for DFS and OAS. The same result was obtained when the model contained ER status and ER-tamoxifen interaction. Indeed, adjuvant tamoxifen significantly prolonged DFS and OAS in c-erbB2-negative cases, whereas it had no effect on DFS and OAS in c-erbB2-positive patients. CONCLUSION: In early-stage breast cancer patients, overexpression of c-erbB2 is a marker of lack of efficacy of adjuvant tamoxifen.

Adult↗

Feasibility and effectiveness of peripheral percutaneous transluminal balloon angioplasty in diabetic subjects with foot ulcers.

OBJECTIVE: The aim of this study was to evaluate the feasibility and effectiveness of this vascular procedure in diabetic inpatients with foot ulcers. RESEARCH DESIGN AND METHODS: In 80 consecutive inpatient diabetic subjects with a foot ulcer, an angiographic study of the lower limbs was carried out to evaluate the necessity and possibility of performing vascular procedures. In 22 subjects, vascular procedure was not necessary; in 26 subjects, peripheral transluminal angioplasty was carried out; in 10 subjects, angioplasty was considered impossible and a peripheral bypass graft was performed; and in 22 subjects, no vascular procedure was considered possible. RESULTS: Of the 26 angioplasties, 8 were performed in iliac or femoral arteries and 18 were performed in the popliteal artery and its branches. The angioplasty was considered unsuccessful in 4 subjects and successful in 22. After angioplasty, on discharge, parameters of limb perfusion improved significantly: transcutaneous oxygen tension was 27.0 +/- 14 mm/Hg on admission and 44.6 +/- 14 mm/Hg on discharge (P < 0.001); ankle-brachial index was 0.61 +/- 0.23 on admission and 0.77 +/- 0.20 on discharge (P = 0.018). Of 22 subjects who underwent successful angioplasty, 21 ended the follow-up of 12 months: during this period, they showed no relapses in the salvaged limb, and their parameters of limb perfusion did not significantly vary. CONCLUSIONS: Angioplasty is feasible in a large percentage of diabetic subjects with peripheral occlusive arterial disease and foot ulcer and is often also practicable in the popliteal artery and its branches. In these subjects, angioplasty significantly improves the parameters of limb perfusion. Angioplasty is therefore an important therapeutic tool in ulcerated diabetic foot care.

Aged↗

Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study.

OBJECTIVE: To evaluate the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer. RESEARCH DESIGN AND METHODS: From August 1993 to August 1995, 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers. All the subjects underwent our diagnostic-therapeutic protocol and were randomized to undergo s-HBOT. Two subjects, one in the arm of the treated group and one in the arm of nontreated group, did not complete the protocol and were therefore excluded from the analysis of the results. Finally, 35 subjects received s-HBOT and another 33 did not. RESULTS: Of the treated group (mean session = 38.8 +/- 8), three subjects (8.6%) underwent major amputation: two below the knee and one above the knee. In the nontreated group, 11 subjects (33.3%) underwent major amputation: 7 below the knee and 4 above the knee. The difference is statistically significant (P = 0.016). The relative risk for the treated group was 0.26 (95% CI 0.08-0.84). The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy: 14.0 +/- 11.8 mmHg in treated group, 5.0 +/- 5.4 mmHg in nontreated group (P = 0.0002). Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT (odds ratio 0.084, P = 0.033, 95% CI 0.008-0.821) and indicated as negative prognostic determinants low ankle-brachial index values (odds ratio 1.715, P = 0.013, 95% CI 1.121-2.626) and high Wagner grade (odds ratio 11.199, P = 0.022, 95% CI 1.406-89.146). CONCLUSIONS: s-HBOT, in conjunction with an aggressive multidisciplinary therapeutic protocol, is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers.

Aged↗

[Primary biliary peritonitis without perforation in childhood: etiopathogenetic evaluations and 2 case reports].

The Authors review biliary peritonitis. After some evaluations on etiopathogenesis, biliary peritonitis without perforation in childhood is discussed. The rarity of this form is considered as well as etiopathological hypothesis, difficulties of diagnosis and surgical management. Two cases of primary biliary peritonitis without perforation observed and operated in two children are reported.

Bile↗

N-Acetyltransferase mechanism for alpha-melanocyte stimulating hormone regulation in rat ageing.

alpha-Melanocyte stimulating hormone (alpha-MSH) is a proopiomelanocortin-derived peptide involved in such behavioural activities as arousal, grooming, memory, learning and attention. Because of these effects, alpha-MSH can be considered the 'adaptation neuropeptide'. Two alpha-MSH major forms were described: acetyl alpha-MSH and des-acetyl alpha-MSH. Since the acetylated form of alpha-MSH is biologically significantly more effective than des-acetyl alpha-MSH, we studied the activity of N-acetyltransferase, the enzyme responsible for MSH acetylation, during ageing in rat hippocampus and pituitary. We observed a substantial decrease of enzyme activity during lifetime, suggesting that the lower synthesis of the more efficient acetylated alpha-MSH form can be related to the reduced adaptive capabilities of aged subjects.

Aging↗