Biomedical subjects

M De Luca

Publications and source records attributed to M De Luca.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease.

Allele epsilon4 of the nuclear APOE gene is a leading genetic risk factor for sporadic Alzheimer's disease (AD). Moreover, an allele-specific effect of APOE isoforms on neuronal cell oxidative death is known. Because of the role of the mitochondrial genome (mtDNA) in oxidative phosphorylation and oxidative stress, an interaction between APOE polymorphism and mtDNA inherited variability in the genetic susceptibility to sporadic AD can be hypothesized. We have explored this hypothesis by analyzing mtDNA germline variants (mtDNA haplogroups) in a sample of AD patients (213 subjects) genotyped for APOE and classified as APOE epsilon4 carriers and non-carriers. We found that the frequency distribution of mtDNA haplogroups is different between epsilon4 carriers and non-carriers (P=0.018), thus showing non-random association between APOE and mtDNA polymorphisms. The same analysis, carried out in two samples of healthy subjects (179 age-matched and 210 individuals aged more than 100 years), showed independence between epsilon4 allele and mtDNA haplogroups. Therefore, the APOE/mtDNA interaction is restricted to AD and may affect susceptibility to the disease. In particular, some mtDNA haplogroups (K and U) seem to neutralize the harmful effect of the APOE epsilon4 allele, lowering the epsilon4 odds ratio from statistically significant to non-significant values.

Aged↗

PubMed2001

Sex-specific longevity associations defined by Tyrosine Hydroxylase-Insulin-Insulin Growth Factor 2 haplotypes on the 11p15.5 chromosomal region.

By studies in centenarians, it was recently found that an STR marker of the Tyrosine Hydroxylase (TH, 11p15.5) gene is associated with human longevity. The aim of the present study was to continue the exploration of the 11p15.5 chromosomal region in human longevity by analyzing two additional RFLP markers, which lie in the Insulin (INS) and Insulin Growth Factor 2 (IGF2) genes. Both the genes, which are localized downstream TH, are indeed good candidates in longevity, as ascertained on the basis of laboratory studies in experimental models. Neither INS nor IGF2 markers did reveal association with longevity. Nevertheless, linkage disequilibrium analyses showed sex-specific longevity associations defined by both TH-INS and TH-IGF2 haplotypes. On the whole, the results reinforce the involvement of the chromosomal region spanning from TH to IGF2 loci in controlling the longevity phenotype in humans.

Adult↗

PubMed2001

HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations.

Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 <P<0.01) difference was found for 5 and 12 alleles, respectively. Four alleles (A*24, A*29, B*27, B*3701) appeared to be essentially "private" Fulani alleles with respect to the other two populations but their presence was not associated with higher resistance to P. falciparum. Our data have then been compared using chord distances (CD) with those from the literature on Africans (including Gambian Fulani) and Caucasoids. The Burkina Faso and Gambian Fulani turned out to be very different (CD=2.191). Moreover, Burkina Faso Fulani were very distant from sympatric Mossi and Rimaibé (CDs=1.912 and 1.884), whereas Gambian Fulani were similar to sympatric Mandinka and Wolof (CDs=0.412 and 0.388) to an extent comparable to that found between Mossi and Rimaibé (CD=0.555). Our study does not suggest the involvement of HLA I in the higher resistance to malaria of Fulani, and confirms a low, if any, Caucasoid component in their gene pool.

Adolescent↗

PubMed2001

Hydrogen peroxide mediates vascular cell adhesion molecule-1 expression from interleukin-18-activated hepatic sinusoidal endothelium: implications for circulating cancer cell arrest in the murine liver.

The mechanism of intrasinusoidal arrest of circulating cancer cells, which is a critical step in liver metastasis, appears to be facilitated by tumor-derived proinflammatory factors that increase sinusoidal cell adhesion receptors for cancer cells. However, how this prometastatic microenvironment is up-regulated remains unknown. Using intrasplenically injected B16 melanoma (B16M) cells, we show that the expression of vascular cell adhesion molecule-1 (VCAM-1) significantly increased in hepatic sinusoidal endothelium (HSE) cells over physiologic baseline within the first 24 hours of metastatic cancer cell infiltration in the liver. This correlated with increased in vitro adhesion of B16M cells to HSE cells isolated from B16M cell-injected mice. In vivo VCAM-1 blockade with specific antibodies before B16M cell injection decreased sinusoidal retention of luciferase-transfected B16M cells by 85%, and metastasis development by 75%, indicating that VCAM-1 expression on tumor-activated HSE cells had a prometastatic contribution. Because VCAM-1 expression is oxidative stress-inducible, recombinant catalase was in vivo administered, resulting in a complete abrogation of both VCAM-1 expression and B16M cell adhesion increases in HSE cells isolated from B16M cell-injected mice. Catalase also abrogated the proadhesive response of HSE cells to B16M-conditioned medium (B16M-CM) in vitro, although this did not affect the concomitant release of major proinflammatory cytokines by HSE cells. HSE cells treated with B16M-CM released interleukin (IL)-18 via tumor necrosis factor-alpha (TNF-alpha)-dependent IL-1beta in vitro. In turn, H(2)O(2) production from B16M-CM-treated HSE cells was regulated by IL-18. Thus, liver-infiltrating B16M cells activated their adhesion to HSE through a sequential process involving TNF-alpha-dependent IL-1beta, which induced IL-18 to up-regulate VCAM-1 via H(2)O(2). The pivotal position of H(2)O(2) was further supported by the fact that incubation of HSE cells with nontoxic concentrations of H(2)O(2) directly enhanced VCAM-1-dependent B16M cell adhesion in vitro without proinflammatory cytokine mediation, which emphasizes the key role of oxidative stress in the pathogenesis of liver inflammation and metastasis.

Animals↗

PubMed2001

Three years experience with the new intragastric balloon, and a preoperative test for success with restrictive surgery.

BACKGROUND: The BioEnterics Intragastric Balloon (BIB) is a smooth, spherical, saline-filled, silicone elastomer with a black radiopaque filling valve, intended to induce weight loss by limiting food consumption. This can be considered a "restrictive" procedure, and by using this balloon, we can assess the patient's eligibility for a restrictive surgical procedure (the BIB-Test). METHODS: From May 1997 to May 2000, 87 BIB were inserted in 77 moderately to severely obese patients (4 BIB in 1 patient, 2 BIB in 7 patients). 64 patients completed the treatment. Out of these, 18 (16 female, 2 male) underwent laparoscopic gastric banding after BIB removal. RESULTS: After the treatment (3-6 months), weight loss results were as follows: WL 14.3 kg, %EWL 23.5 and loss in BMI 5.3. 12 patients after the preliminary BIB, have been followed > or = 6 months after gastric banding, and have significant further weight loss. CONCLUSIONS: BIB appears to have good results. A supervised nutritional and behavioral regimen is mandatory. The balloon may be indicated to: 1) induce weight loss in patients whose obesity is not severe enough to warrant surgery; 2) reduce the surgical risk in those who are massively obese; 3) select patients for gastric restrictive surgery if they lose weight with the balloon. The data showed that patients who had good results with the BIB (positive BIB-Test) are still losing weight after subsequent gastric banding.

Adult↗

PubMed2001

Comparison of calcium sulfate and autogenous bone graft to bioabsorbable membranes plus autogenous bone graft in the treatment of intrabony periodontal defects: a split-mouth study.

BACKGROUND: Current literature shows that calcium sulfate can be used in guided tissue regeneration. Its biocompatibility and resorbability give it significant advantages in the treatment of periodontal and endodontic defects. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change, beyond that achieved with debridement alone, in treating intraosseous defects. The aim of the present investigation was to evaluate the clinical results obtained with autologous bone plus calcium sulfate, and to compare them with the results obtained using autologous bone plus membrane. METHODS: A total of 12 patients were treated in the present investigation. A split-mouth design was utilized. Twelve 3-wall periodontal defects were treated with calcium sulfate plus autologous bone graft (test) and compared with 12 contra-lateral defects treated with a bioabsorbable membrane plus autologous bone graft (control). Before the surgical procedure, patients were instructed about oral hygiene and scaling and root planing (SRP) was completed. Probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded at baseline and 6 months. RESULTS: There were no statistical differences between test and control defects at baseline. BOP was 58% and 50% for control and test defects, respectively. Mean PD was 7.75+/-0.96 mm (control) and 8.0+/-1.28 mm (test). Mean CAL was 8.58+/-1.31 mm (control) and 8.83+/-0.91 mm (test). At 6 months, mean PD was 3.41+/-0.51 (P = 0.0022) for control defects and 3.58+/-0.51 (P = 0.0022) for test defects. CAL showed a mean gain of 5+/-0.85 for controls (P = 0.0022) and 5.25+/-0.75 for test defects (P = 0.0022). Thus, there was a mean reduction of PD of 4.33 mm (56%) for control sites and 4.42 mm (55%) for test sites. The mean clinical attachment gain was 3.57 mm for control sites and 3.58 mm for test sites. As there were no sham-operated controls, it is not clear that the healing of these test or control-treated sites was any better than similar 3-walled defects sham operated. CONCLUSIONS: Both therapies led to short-term improvement of the measured parameters; neither was superior to the other.

Absorbable Implants↗

PubMed2001

[Antibiotic and immunostimulating prophylaxis in colorectal surgery].

The Authors, after considering post-operatory sepsis as cause of failures and as an important economic damage, make among them a distinction according to the arising area and to the seriousness of their manifestations. They, later, describe corrective and prophylactic measures which in colo-rectal surgery ase campulsory assumptions for sepsis prevention. After relating their experience, Authors reaffirm short-term protocol validity and point out validity of alternation of large spectrum molecules in order to avoid possible arising of bacterial resistances.

Aged↗

PubMed2000

Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by a severe reduction of visual acuity, hypopigmentation of the retina and the presence of macromelanosomes in the skin and eyes. Various types of mutation have been identified within the OA1 gene in patients with the disorder, including several missense mutations of unknown functional significance. In order to shed light into the molecular pathogenesis of ocular albinism and possibly define critical functional domains within the OA1 protein, we characterized 19 independent missense mutations with respect to processing and subcellular distribution on expression in COS-7 cells. Our analysis indicates the presence of at least two distinct biochemical defects associated with the different missense mutations. Eleven of the nineteen OA1 mutants (approximately 60%) were retained in the endoplasmic reticulum, showing defecNStive intracellular transport and glycosylation, consistent with protein misfolding. The remaining eight of the nineteen OA1 mutants (approximately 40%) displayed sorting and processing behaviours indistinguishable from those of the wild-type protein. Consistent with our recent findings that OA1 represents a novel type of intracellular G protein-coupled receptor (GPCR), we found that most of these latter mutations cluster within the second and third cytosolic loops, two regions that in canonical GPCRs are known to be critical for their downstream signaling, including G protein-coupling and effector activation. The biochemical analysis of OA1 mutations performed in this study provides important insights into the structure-function relationships of the OA1 protein and implies protein misfolding as a major pathogenic mechanism in OA1.

Albinism, Ocular↗

PubMed2000

Toward epidermal stem cell-mediated ex vivo gene therapy of junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a group of severe, inherited skin diseases caused by mutations in the genes encoding laminin 5 or other components of the hemidesmosome. Since human epidermis is a self-renewing tissue, gene therapy of JEB requires the stable integration of the transgene into the genome of the epidermal stem cell. Human epidermal stem cells can indeed be cultivated and stably transduced with replication-defective retroviral vectors, allowing full phenotypic correction of the adhesion properties of JEB keratinocytes. Epidermal stem cells generate cohesive sheets of stratified epithelium suitable for the permanent coverage of massive skin defects, and genetically modified epidermal sheets maintain long-term expression of the transgene after transplantation on immunodeficient animals. Moreover, we have developed a clinical procedure that allows transplantation of cultured epidermal sheets on large body areas under local anesthesia and without cicatricial outcomes. Thus, (1) the possibility of cultivating lining epithelia, (2) the availability of noninvasive surgical procedures that allow the grafting of large skin areas, and (3) the demonstration of sustained transgene expression in vitro and in vivo by epidermal stem cells, prompt us to propose the implementation of a phase I/II clinical trial aimed at the ex vivo gene therapy of selected JEB patients. The aim of the trial is to validate the ex vivo procedure in a clinical setting, to prove its overall safety, and to analyze critical issues such as long-term survival of the genetically modified implant, immune response against the transgene product, and persistence of transgene expression at therapeutic levels.

Cells, Cultured↗

PubMed2000

Downregulation of 14-3-3sigma prevents clonal evolution and leads to immortalization of primary human keratinocytes.

In human epidermal keratinocytes, replicative senescence, is determined by a progressive decline of clonogenic and dividing cells. Its timing is controlled by clonal evolution, that is, by the continuous transition from stem cells to transient amplifying cells. We now report that downregulation of 14-3-3sigma, which is specifically expressed in human stratified epithelia, prevents keratinocyte clonal evolution, thereby forcing keratinocytes into the stem cell compartment. This allows primary human keratinocytes to readily escape replicative senescence. 14-3-3sigma-dependent bypass of senescence is accompanied by maintenance of telomerase activity and by downregulation of the p16(INK4a) tumor suppressor gene, hallmarks of keratinocyte immortalization. Taken together, these data therefore suggest that inhibition of a single endogenous gene product fosters immortalization of primary human epithelial cells without the need of exogenous oncogenes and/or oncoviruses.

14-3-3 Proteins↗

PubMed2000

Structure and function of the von Willebrand factor A1 domain: analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation.

Binding of the adhesive glycoprotein, von Willebrand factor (vWf), to the platelet membrane glycoprotein (GP) Ib-IX-V complex initiates platelet adhesion and aggregation at high shear stress in hemostasis and thrombosis. In this study, the GP Ib-IX-V binding site within the vWf A1 domain was analyzed using a panel of murine monoclonal antibodies raised against a 39/34-kd vWf fragment (Leu-480/Val-481-Gly-718) encompassing the A1 domain. One antibody, 6G1, strongly inhibited ristocetin-dependent vWf binding to platelets, but had no effect on botrocetin- or jaracetin-dependent binding, or asialo-vWf-dependent platelet aggregation. The 6G1 epitope was mapped to Glu-700-Asp-709, confirming the importance of this region for modulation of vWf by ristocetin. Like ristocetin, 6G1 activated the vWf A1 domain, because it enhanced binding of the 39/34-kd fragment to platelets. In contrast, 5D2 and CR1 completely inhibited asialo-vWf-induced platelet aggregation and ristocetin-induced vWf binding to GP Ib-IX-V. However, only 5D2 blocked botrocetin- and jaracetin-induced vWf binding to platelets and binding of vWf to botrocetin- and jaracetin-coated beads. Epitopes for 5D2 and CR1 were conformationally dependent, but not congruent. Other antibodies mapped to epitopes within the A1 domain (CR2 and CR15, Leu-494-Leu-512; CR2, Phe-536-Ala-554; CR3, Arg-578-Glu-596; CR11 and CR15, Ala-564-Ser-582) were not functional, identifying regions of the vWf A1 domain not directly involved in vWf-GP Ib-IX-V interaction. The combined results provide evidence that the proline-rich sequence Glu-700-Asp-709 constitutes a regulatory site for ristocetin, and that ristocetin and botrocetin induce, at least in part, separate receptor-recognition sites on vWf. (Blood. 2000;95:164-172)

Amino Acid Sequence↗

PubMed2000

Treatment of "stable" vitiligo by Timedsurgery and transplantation of cultured epidermal autografts.

OBJECTIVE: To optimize melanocyte/keratinocyte co-cultivation and to evaluate the effectiveness of autologous cultured epidermal grafts in the surgical treatment of stable vitiligo. DESIGN: After optimization of melanocyte/keratinocyte cultures, achromic lesions were disepithelialized by means of programmed diathermosurgery (Timedsurgery) and covered with autologous epidermal grafts prepared from secondary cultures. Melanocyte content was evaluated by dopa reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. SETTING: A biosafety level 3 cell culture facility and a dermatological department in a hospital. PATIENTS: Thirty-two patients carrying different types of vitiligo were admitted to the study and treated with autologous cultured epidermal grafts. Inclusion criteria were (1) failure of at least 2 standard medical approaches; (2) no therapy for at least 12 months; (3) absence of progression of old lesions, absence of appearance of new lesions, and absence of Koebner phenomenon within the past 18 months; and (4) absence of autoimmune disorders. RESULTS: One hundred five achromic lesions (a total of 6078.2 cm(2)) were treated. The average percentage of repigmentation, evaluated after 12 to 36 months of follow-up, was 77%. Independent of the type of vitiligo, average percentages of repigmentation of extremities and periorificial sites were 8% (31.8 cm(2) repigmented/420.5 cm(2) transplanted) and 35% (17.6 cm(2) repigmented/50.0 cm(2) transplanted), respectively. Percentages of repigmentation of all other body sites ranged from 88% to 96% (4329.7 cm(2) repigmented/4675.2 cm(2) transplanted). Color matching was good and scar formation was not observed. CONCLUSION: Cultured epidermal grafts can be considered a real therapeutic surgical alternative for "stable" but not lip-tip vitiligo.

Adolescent↗

PubMed2000

Solitary necrotic nodule of the liver misinterpreted as malignant lesion: considerations on two cases.

In our experience, we document 2 cases of a rare and non-tumoral lesion of the liver misinterpreted as necrotic tumor: necrotic solitary nodule. In the first clinical case, ultrasound (US) showed a polylobated lesion (35 x 35 x 38 mm) at segment 8. Color-doppler identified a compression of celiac axis (Dunbar syndrome). Arteriography revealed a subtotal stenosis of celiac tripod soon after the emergence of the left gastric artery. FNAB-CT showed a highly cellulated tissue with a necrotic core surrounded by a fibersclerotic tissue. The patient underwent surgery: cholecystectomy and correction of Dunbar syndrome. US follow-up showed a progressive reduction in diameter of the lesion (24 x 25 x 25 mm at 24 months), suggesting in this case the role of ischemic injury in the pathogenesis of the lesion. In the second clinical case, a hypoechoic lesion (32 x 32 x 30 mm) of segment 6 as occasional US finding during the staging for prostate cancer was shown. FNAC-CT showed a positive result for necrotic cells. Surgical treatment consisted in a wide excision of the lesion. Histologically the lesion was solitary necrotic nodule. The diagnosis of this rare lesion is accidental. In accordance with the literature (50% of cases), we founded an associated tumor. Radiology doesn't differentiate solitary necrotic nodule and other solid lesions. Diagnosis is histological (in our second case, FNAC-CT misinterpreted the tumor as a malignant lesion, while histology showed the real nature of it).

Adult↗

PubMed2000

Screening of the municipal water system of La Plata, Argentina, for human intestinal parasites.

The La Plata River, though severely contaminated by intestinal parasites through the discharge of tons of crude fecal material from a main sewage channel, nevertheless provides drinking water to two-thirds of La Plata, Argentina, after conventional purification at a processing plant. With intestinal parasitosis being endemic here, we investigated the importance of this water in transmitting such pathogens to the city's populace by means of standard methodology for sample acquisition and processing involving filter-concentration of waterborne particulates. Of 14 tap-water samples collected from the distribution network, 12 pertained to four zones (A-D) within the city center; while the remaining 2 were obtained near the processing plant, 15 kilometers outside the city. Although parasites were found within the samples derived from the four urban zones, none were detected in the specimens obtained near the plant. The four downtown areas differed from each other as to the quantity and nature of the parasites present in their water: whereas zones A and B registered similar lower levels of contaminants, C and D exhibited higher values significantly different from the former two and from each other. Given an average parasite count/l citywide of 0.38 and a probability of encountering a parasite within 11 of water of 0.32, the municipal network is seen to contribute to the transmission of intestinal parasites. A routine system of water-quality control is therefore needed throughout the city along with the establishment of infrastructures for locating and eliminating peripheral sources of contamination.

Animals↗

PubMed2000

Genes and longevity: lessons from studies of centenarians.

In population studies of aging, the data on genetic markers are often collected for individuals from different age groups. The idea of such studies is to identify "longevity" or "frailty" genes by comparing the frequencies of genotypes in the oldest and in the younger groups of individuals. In this paper we discuss a new approach to the analysis of such data. This approach, based on the maximum likelihood method, combines data on genetic markers with survival information obtained from standard demographic life tables. This method allows us to evaluate survival characteristics for individuals carrying respective candidate genes. It can also be used in the estimation of the effects of allele-area and allele-allele interaction, either in the presence or absence of hidden heterogeneity. We apply this method to the analysis of Italian data on genetic markers for five autosomal loci and mitochondrial genomes. Then we discuss basic assumptions used in this analysis and directions of further research.

Aged↗

PubMed2000

Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors.

The discoidin domain receptor (DDR1) is characterized by a discoidin I motif in the extracellular domain, an unusually long cytoplasmic juxtamembrane (JM) region, and a kinase domain that is 45% identical to that of the NGF receptor, TrkA. DDR1 also has a major splice form, which has a 37 amino acid insert in the JM region with a consensus Shc PTB site that is lacking in the shorter receptor. One class of ligands for the DDR receptors has recently been identified as being derived from the collagen family, but neither native PC12 cells, which express modest amounts of DDR1, nor transfected PC12 cells, which express much larger amounts of DDR1, respond to this ligand. A chimeric receptor, containing the extracellular domain of hPDGFRbeta fused to the transmembrane and intracellular regions of DDR1, also fails to mediate neuronal-like differentiation in stably transfected PC12 cells and is only weakly autophosphorylated. However, chimeric receptors, which are composed of combinations of intracellular regions from DDR1 and TrkA (with the extracellular domain of hPDGFRbeta), in some cases provided ligand (PDGF) -inducible receptor responses. Those with the TrkA kinase domain and the DDR1 JM regions were able to produce differentiation to varying degrees, whereas the opposite combination did not. Analysis of the signaling responses of the two chimeras with DDR1 JM sequences (with and without the insert) indicated that the shorter sequence bound and activated FRS2 whereas the insert-containing form activated Shc instead. Both activated PLCgamma through the carboxyl-terminal tyrosine of the TrkA domain (Y785 in TrkA residue numbering). Mutation of this site (Y-->F) eliminated PLCgamma activation (indicating there are no other cryptic binding sites for PLCgamma in the DDR1 sequences) and markedly reduced the differentiative activity of the receptor. This is in contrast to TrkA (or PDGFRbeta/TrkA chimeras), where ablation of this pathway has no notable effect on PC12 cell morphogenic responses. Thus, the activation of FRS2 and Shc (leading to MAPK activation) is weaker in the DDR1/TrkA chimeras than in TrkA alone, and the PLCgamma contribution becomes essential for full response. Nonetheless, both DDR1 JM regions contain potentially usable signaling sites, albeit they apparently are not activated directly in DDR1 (or DDR1 chimeras) in a ligand-dependent fashion. These findings suggest that the DDR1 receptors do have signaling capacity but may require additional components or altered conditions to fully activate their kinase domains and/or sustain the activation of the JM sites.

Animals↗

PubMed2000

Inflamm-aging. An evolutionary perspective on immunosenescence.

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

Aging↗

PubMed2000

Laparotomic vs laparoscopic lap-band: 4-year results with early and intermediate complications.

BACKGROUND: Adjustable banding is safe, low invasive, and effective for losing weight. METHODS: 69 patients underwent this procedure by laparotomy or laparoscopy. RESULTS: Patients operated by laparotomy lost more weight than those operated by laparoscopy, but in 4 patients we were forced to re-operate in order to remove the band (3 pouch dilatations and 1 stomach slippage), and in 9 patients a ventral hernia appeared (5 patients repaired). In the laparoscopic cases there were 4 intra-operative gastric perforations, but all were repaired and the band placed at the same time (3 conversions to open), causing an increased post-operative hospital stay. There was a lower limb deep venous thromboembolism, which was followed by fatal pulmonary embolism (although the patient had been given heparin and had been treated with elastocompression and mobilization 2 hours after surgery). The band eroded in one patient. Weight losses in these morbidly obese patients were satisfactory at 2 years and maintained beyond 3 years. CONCLUSION: Laparoscopic adjustable banding is an efficient, generally safe procedure.

Adult↗