Soft tissue regeneration in animal models using grafts from adipose mesenchymal stem cells and peripheral blood fibrin gel.

OBJECTIVE: Our study aimed to evaluate the effect of soft tissue regeneration in nude mice using grafts made from the combination of adipocytes from fat tissue mesenchymal stem cells and fibrin gel from peripheral blood. MATERIALS AND METHODS: Mesenchymal stem cells were isolated from adipose tissue and identified according to ISCT criteria. The scaffold used was fibrin obtained from peripheral blood. The grafts in this study were generated by transferring mesenchymal stem cells onto a fibrin scaffold. Two types of grafts, the research sample (fibrin scaffold containing adipocytes differentiated from mesenchymal stem cells) and the control sample (fibrin scaffold only), were grafted under the dorsal skin of the same mouse. After each research period, samples were collected and evaluated by histological methods to observe the existence and growth of cells inside the grafts. RESULTS: The results showed that the study group's graft integrated better within the tissue when compared with the control group. In addition, the grafts in the study group showed the presence of cells with characteristic morphology of adipocytes one week after transplantation. In contrast, control samples showed dimorphous shapes and features mainly composed of non-homogenous fragments. CONCLUSIONS: These initial conclusions might be considered a first step in generating safe bio-compatible engineered grafts specifically usable in post-traumatic tissue regeneration procedures.

Rethinking vulnerability in city-systems: A methodological proposal to assess "urban entropy".

This paper aims at proposing a possible alternative point of view to investigate the vulnerability of urban systems. The basic ideal refers to the possibility of thinking about vulnerability as deriving by the interactions of several risks that can affect the urban system and by the interactions among them. In this sense, it is possible to refer to an "integrated territorial risk". Considering the city as a complex and dynamic system that while evolving produce entropy is the main theoretical reference supporting this study. The loss of energy during the evolution of the system corresponds to some conditions of inefficiency that involve the whole system and, as such, this lost energy can be assumed as a "systemic entropy". Is it possible to measure the levels of this vulnerability of the urban system when it stays in ordinary conditions, namely not during stress states that modify the state of equilibrium of the system itself? It is possible to assess the production of this "internal entropy"? In order to answer to these questions in mind, this study aims at analyzing dyscrasias that can occur within the main components of the urban system in order to individuate possible strategies able both to mitigate the fragility of the urban system and to improve its resilience.

Bladder function associated with posterior urethral valves after primary valve ablation or proximal urinary diversion in children and adolescents.

PURPOSE: We retrospectively reviewed 2 series of patients with posterior urethral valves treated initially with valve ablation preceded by bilateral cutaneous ureterostomies or valve ablation alone to evaluate and compare bladder function behavior of each treatment group. MATERIALS AND METHODS: From 1970 to 1983, 19 males 22 days to 21 months old with posterior urethral valves were treated with 1 of 2 initial surgical approaches, including upper tract diversion, delayed undiversion and ablation in 11 (group 1), and primary valve ablation only in 8 (group 2). Median patient age at the time of cutaneous urinary diversion and primary valve ablation for groups 1 and 2 was 7 and 9 months, respectively. Median duration of bladder defunctionalization was 48 months. All patients were evaluated urodynamically after initial ablation or re-functionalization of the bladder using standard rapid fill cystometry. Median patient age for groups 1 and 2 was 14 and 9.5 years, respectively, at the time of urodynamic testing 16 and 12.6 years, respectively, at followup. RESULTS: Urodynamic assessment revealed detrusor instability in 5 group 1 patients but in only group 2 1 patient. Group 2 patients had significantly lower median end filling pressure (4 versus 15 cm. water, p <0.03) and higher maximum bladder capacity (1.4 versus 0.8, p <0.005) than those in group 1. Group 1 patients had lower compliance than those in group 2 (median 15 versus 82 cm. water, p <0.05). Further analysis showed no difference between groups 1 and 2 in overall median voiding detrusor pressure at maximum flow (51 versus 52.6 cm. water, respectively). Cystometric detrusor under activity patterns were noted in 5 group 1 and 2 group 2 patients. Residual urine volumes were 17%, 31%, 19% and 8% of bladder capacity, respectively, in 2 group 1 and 2 group 2 patients. At final followup 5 group 1 and 2 group 2 patients had renal function deterioration. Two other group 1 patients and group 2 had progression to end stage renal failure. A higher ureteral reimplantation rate was noted in group 1 (63%) than group 2 (6%). CONCLUSIONS: This retrospective study revealed that long-term bladder function of patients with posterior urethral valves treated with temporary supravesical diversion is affected more adversely than those treated with valve ablation alone.

Urodynamic findings in boys with posterior urethral valves after treatment with primary valve ablation or vesicostomy and delayed ablation.

PURPOSE: Primary valve ablation and temporary vesicostomy with delayed valve ablation are alternative initial management procedures in neonates and infants with posterior urethral valves. To investigate whether initial vesicostomy followed by delayed valve ablation and simultaneous vesicostomy closure may lead to more alterations in bladder function than primary valve ablation only we retrospectively compared postoperative urodynamic findings in 2 small groups of patients. MATERIALS AND METHODS: From 1980 to 1990, 15 male infants 19 days to 34 months old with posterior urethral valves were treated with 1 of 2 initial surgical approaches, including valve ablation only in 8 (group 1), and primary vesicostomy and delayed valve ablation associated with concomitant vesicostomy closure in 7 (group 2). Mean age at valve ablation and vesicostomy in groups 1 and 2 was 10.8 +/- 11.2 months (range 1 to 35) and 55.4 +/- 43.3 days (range 19 to 151), respectively. Average duration of vesicostomy diversion was 33.6 +/- 18.8 months (range 14 to 70). All patients underwent conventional urodynamics postoperatively using normal saline at room temperature. In groups 1 and 2 mean age at followup was 11.5 +/- 6.6 (range 5 to 16.2) and 9. 4 +/- 3.1 (range 4.10 to 14) years, respectively. Controls comprised 46 age matched males who underwent urodynamics using similar methodology. RESULTS: Postoperative urodynamic assessment of maximum cystometric bladder capacity and the incidence of detrusor instability in each treatment group were not statistically different. In group 1 bladder capacity was significantly higher than that in controls (p <0.0001). In group 2 mean end filling detrusor pressure was increased compared with that in group 1 (29 cm. water, range 15 to 60 versus 8, range 4 to 21). Compliance was significantly lower in group 2 than in group 1 (p <0.0005). Analysis of detrusor voiding pressure at maximum flow was not significantly different in the 2 groups. We noted detrusor under activity in 1 group 1 and 2 group 2 cases. In these patients post-void residual urine volume was 8% to 66% of cystometric bladder capacity. However, only 1 of these 3 patients who required augmentation cystoplasty needed intermittent catheterization. Urodynamic patterns of outflow obstruction developed in 1 patient in each group, including urethral stricture and bladder neck obstruction. At followup we observed no difference in renal function impairment in the 2 groups. CONCLUSIONS: Our retrospective study of rapid filling cystometry suggests that primary valve ablation for posterior urethral valves is associated with a better bladder function outcome than that in patients treated with vesicostomy and delayed valve ablation. Therefore, although cutaneous vesicostomy may be performed as initial management of posterior urethral valves, primary valve ablation is the most effective surgical option in these cases.

Localization of adipocyte long-chain fatty acyl-CoA synthetase at the plasma membrane.

Long-chain fatty acyl-CoA synthetase (FACS) catalyzes esterification of long-chain fatty acids (LCFAs) with coenzyme A (CoA), the first step in fatty acid metabolism. FACS has been shown to play a role in LCFA import into bacteria and implicated to function in mammalian cell LCFA import. In the present study, we demonstrate that FACS overexpression in fibroblasts increases LCFA uptake, and overexpression of both FACS and the fatty acid transport protein (FATP) have synergistic effects on LCFA uptake. To explore how FACS contributes to LCFA import, we examined the subcellular location of this enzyme in 3T3-L1 adipocytes which natively express this protein and which efficiently take up LCFAs. We demonstrate for the first time that FACS is an integral membrane protein. Subcellular fractionation of adipocytes by differential density centrifugation reveals immunoreactive and enzymatically active FACS in several membrane fractions, including the plasma membrane. Immunofluorescence studies on adipocyte plasma membrane lawns confirm that FACS resides at the plasma membrane of adipocytes, where it co-distributes with FATP. Taken together, our data support a model in which imported LCFAs are immediately esterified at the plasma membrane upon uptake, and in which FATP and FACS function coordinately to facilitate LCFA movement across the plasma membrane of mammalian cells.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part II.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus simultaneously on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain. This part examines pharmacologic methods.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part I.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care, and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain.

Insulin delivery in nosedrops: new formulations containing alkylglycosides.

Insulin was administered to rats via nosedrops in the presence or absence of various alkylglycosides; systemic insulin absorption was measured as a fall in blood D-glucose concentration in animals made hyperglycemic by xylazine/ketamine anesthesia. Nosedrops (0.04 ml) containing alkylglycosides or regular porcine insulin alone were without effect. Nosedrops containing both a small amount of alkylglycoside (0.03-0.50%) and insulin (2 U regular porcine) caused a rapid decrease in blood D-glucose levels and a concomitant increase in serum immunoreactive insulin levels. The maximal hypoglycemic response was observed between 60 and 120 min after delivery of nosedrops. Decylmaltoside was less effective at enhancing systemic insulin absorption than dodecylmaltoside, tridecylmaltoside, or tetradecylmaltoside, whereas octylmaltoside was totally ineffective. Dodecylsucrose, a compound which differs from dodecylmaltoside only in one carbohydrate residue, had a similar effect on blood D-glucose values when it was included in the nosedrop formulation with insulin. Decylsucrose was considerably less potent than dodecylsucrose at enhancing systemic absorption of insulin. Nonylglucoside was effective at promoting insulin absorption from nosedrops only when used at higher doses (0.25-0.50%), whereas heptylglucoside and hexylglucoside were ineffective. These results indicated that nosedrops containing insulin plus an extremely low concentration (0.03%) of an absorption-enhancing agent such as tetradecylmaltoside can be used to lower blood D-glucose values.

Efficacy of insulin eyedrops.

Systemic absorption of insulin delivered via eyedrops has been studied in rats made transiently hyperglycemic by anesthesia with xylazine/ketamine. Insulin at a concentration of 2 mg/ml was not absorbed significantly when saline alone was used as the formulation for the eyedrops (0.04 ml). When various emulsant agents were added to the eyedrop formulation, systemic insulin levels were increased and concomitantly, blood D-glucose levels were decreased. Saponin, Brij-78, BL-9 and several alkylglycosides all increased the systemic absorption of insulin following delivery in eyedrops. Not all surfactant agents were effective in promoting systemic insulin absorption from eyedrops, as evidenced by the failure of some non-ionic surfactants to increase insulin absorption. Similar results were obtained when nosedrops containing insulin plus non-ionic surfactants were administered to rats. In conclusion, systemic insulin absorption was greatly accelerated by the addition of certain emulsants to the eyedrop formulation and physiologically important levels of insulin could be delivered systemically following eyedrop administration.