The Association between Dietary Inflammatory Index and Aging Biomarkers/Conditions: A Systematic Review and Dose-response Meta-analysis.

OBJECTIVES: We performed a current study to examine the association between dietary inflammatory index (DII) score and older age-related muscle conditions, including sarcopenia, low muscle mass, low muscle strength, frailty, and/or disability. DESIGN: Systematic review and dose-response meta-analysis. SETTING: A systematic literature search was performed using Scopus, PubMed/MEDLINE, and ISI Web of Science without limitation until October 04, 2022. Relative risk (RR) and 95% confidence interval (CI) were pooled by applying a random-effects model, while validated methods examined assess quality and publication bias via Newcastle-Ottawa Scale, Egger's regression asymmetry, and Begg's rank correlation tests respectively. A dose-response meta-analysis was conducted to estimate the RRs per 1-unit increment in DII scores. PARTICIPANTS: Adults (≥18 years). MEASURES: The risk of older age-related muscle conditions (sarcopenia, low muscle mass, low muscle strength, frailty, and/or disability). RESULTS: Data were available from 19 studies with 68079 participants. Results revealed that a higher DII score was significantly related to an increased risk of sarcopenia (RR=1.50; 95% CI: 1.26, 1.79; I2=53.3%; p<0.001; n=10; sample size =43097), low muscle strength (RR=1.47; 95% CI: 1.24, 1.74; I2=6.6%; p<0.001; n=4; sample size =9339), frailty (RR=1.61; 95% CI: 1.41, 1.84; I2=0.0%; p<0.001; study=5; participant=3882) and disability (RR=1.41; 95% CI: 1.16, 1.72; I2=58.4%; p=0.001; n=5; sample size =13760), but not low muscle mass (RR=1.24; 95% CI: 0.98, 1.56; I2=49.3%; p=0.069; n=4; sample size =11222). Additionally, results of the linear dose-response indicated that an increase of one point in the DII score was related to a 14% higher risk of sarcopenia, 6% higher risk of low muscle mass, 7% higher risk of low muscle strength, and a 7% higher risk of disability in adults. Non-linear dose-response relationships also revealed a positive linear association between the DII score and the risk of sarcopenia (Pnonlinearity = 0.097, Pdose-response<0.001), frailty (Pnonlinearity = 0.844, Pdose-response=0.010) and disability (Pnonlinearity = 0.596, Pdose-response=0.007). CONCLUSION: Adherence to a pro-inflammatory diet was significantly associated with a higher risk of sarcopenia and other age-associated adverse effects such as low muscle strength, disability, and frailty. These results indicate a necessity to prioritize the reduction of pro-inflammatory diets to help promote overall older age-related muscle conditions.

Dynamics of coherent activity between cortical areas defines a two-stage process of top-down attention.

Analysing a visual scene requires the brain to briefly keep in memory potentially relevant items of that scene and then direct attention to their locations for detailed processing. To reveal the neuronal basis of the underlying working memory and top-down attention processes, we trained macaques to match two patterns presented with a delay between them. As the above processes are likely to require communication between brain regions, and the parietal cortex is known to be involved in spatial attention, we simultaneously recorded neuronal activities from the interconnected parietal and middle temporal areas. We found that mnemonic information about features of the first pattern was retained in coherent oscillating activity between the two areas in high-frequency bands, followed by coherent activity in lower frequency bands mediating top-down attention on the relevant spatial location. Oscillations maintaining featural information also modulated activity of the cells of the parietal cortex that mediate attention. This could potentially enable transfer of information to organize top-down signals necessary for selective attention. Our results provide evidence in support of a two-stage model of visual attention where the first stage involves creating a saliency map representing a visual scene and at the second stage attentional feedback is provided to cortical areas involved in detailed analysis of the attended parts of a scene.

Ecotoxicological risk of polycyclic aromatic hydrocarbons (PAHs) in urban soil of Isfahan metropolis, Iran.

Concentration, distribution, probable sources, and health risks of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated in 52 soil samples collected within a radius 50 km from Isfahan metropolis center. Total concentration of PAHs ranged from 57.70 to 11,730.08 µg/kg averaging 2,000.56 µg/kg. Spatial PAH profiles were site-specific and higher concentration of PAHs was observed in the vicinity of industrial zones within Isfahan metropolis. The molecular indices, ring classes, and principal component analysis indicated that the sources of PAHs were both geogenic and pyrogenic. The incremental lifetime cancer risks of exposure to soil PAHs for adults and children living in the study area were 2.3×10(-2) and 2.2×10(-3), respectively. The results suggest that current PAHs levels in Isfahan metropolis soil are highly carcinogenic and may hold a serious health risk for local resident.

Optimizing culture media for in vitro proliferation and rooting of Tetra (Prunus empyrean 3) rootstock.

The enormous demand for new rootstock genotypes in Prunus spp. makes us to use micropropagation as an unavoidable propagation method. Therefore, the study on micropropagation of a new semi-dwarf vegetative rootstock namely Tetra (Prunus empyrean 3) was carried out to develop an optimized protocol. Culture establishment using nodal segments was enhanced using WPM (woody plant medium) medium lacking growth regulators. From various shoot multiplication treatments, the highest number of shoots per explant (30.4) was found on ME (Media created specifically) medium supplemented with 0.8 mg l-1 BAP and 0.05 mg l-1 IBA. 100% in vitro rooting was achieved on ½ strength MS medium with 0.5 mg l-1 IBA, 1.6 mg l-1 thiamine and 150 mg l-1 iron sequestrene.

Gastric acid secretion induced by paraventricular nucleus microinjection of orexin A is mediated through activation of neuropeptide Yergic system.

UNLABELLED: Very recently, we have reported that the modulatory effect of PVN on gastric acid secretion may be mediated through the orexin fibers and/or orexin-responsive neurons. In this study, we address the hypothesis which demonstrates the existence of a putative orexin A - neuropeptide Y Y1/Y5 receptors interaction to increase gastric acid secretion in pyloric-ligated conscious rats. Male Wistar rats were implanted with guide canula directed to the PVN and lateral ventricle. Intracerebroventricular (ICV) microinjections of GR-231118 (Y1 receptor antagonist) and CGP-71683 (Y5 receptor antagonist) on gastric acid secretion were considered. The effect of pretreatment with Y1 receptor antagonist, GR-231118, and Y5 receptor antagonist, CGP-71683, on PVN orexin A-induced acid secretion was assessed. Gastric acid secretion was measured using the pylorus-ligation method, and the amount of gastric acid was determined by titration with 0.01N NaOH to a pH of 7.0. KEY RESULTS: ICV microinjections of GR-231118 and CGP-71683 decreased acid secretion by 25±0.05% and 67±0.02%, respectively. ICV microinjections of GR-231118 and CGP-71683 inhibited effects of PVN-injected orexin-A on acid secretion. We suggest that Y1 and Y5 receptors stimulate gastric acid secretion and the stimulatory effect of PVN orexin receptors on gastric acid secretion may be mediated via interactions, at least in part, through activation of Y1 and Y5 receptors. These neural pathways may play key roles in the orexinergic action of orexins in the cephalic phase of gastric acid secretion.

Synthesis and antinociceptive behaviors of new methyl and hydroxyl derivatives of phencyclidine.

Phencyclidine (I) and its derivatives show such pharmacological behaviors as analgesic, anticonsulvant, anti-anxiety and antidepressant, while interacting with central nervous system. In this study, new methyl and hydroxyl derivatives of PCP were synthesized and their antinociceptive behaviors in animals were examined by measuring the number of writhing in a writhing test of visceral pain and the pain scores in Formalin test. Compared to control and PCP groups, findings in experimental groups indicated the new synthesized analogues (compounds II, III and V, 10 mg/kg) of PCP were able to produce more analgesic effects in formalin and writhing tests, especially for compound V. It was concluded that the new synthesized derivatives of PCP could substantially and respectively diminish acute and chronic pains.

Effects of orexin and glucose microinjected into the hypothalamic paraventricular nucleus on gastric acid secretion in conscious rats.

BACKGROUND: Orexin-A is a novel peptide that appears to play a role in regulation of gastric acid secretion. However, little is known about sites of its action. In addition, evidences suggest that some of orexin-A neurons respond to glucose. In this study, we address the hypothesis which demonstrates that orexin-A and glucose act in the hypothalamic paraventricular nucleus (PVN) to increase gastric acid secretion and juice volume in pyloric-ligated conscious rats. METHODS: Male Wistar rats were implanted with guide canula directed to the PVN. Orexin-A (3-10 µg), glucose (350-750 ng) SB334867 (6-20 µg) were microinjected. The effect of pretreatment with an orexin-1 receptor antagonist, SB334867, on orexin-A and D-glucose induced acid secretion was assessed. Gastric acid secretion was measured using the pylorus-ligation method, and the amount of gastric acid was determined by titration with 0.01 N NaOH to a pH of 7.0. KEY RESULTS: Intraparaventricular injection of orexin-A or D-glucose stimulated gastric acid secretion in a dose-dependent manner. The PVN injections of orexin-A receptor antagonist, SB334867, were associated with gastric acid secretion decrease and inhibited effects of PVN-injected orexin-A. Orexin-stimulated gastric acid secretion was decreased (~40%) after PVN lesions. Glucose-stimulated gastric acid secretion was also suppressed by intraperitoneal (IP) injection of SB334867. In addition, it was observed that co-injection of orexin-A and glucose at ineffective doses increased gastric secretion significantly. CONCLUSIONS & INFERENCES: We suggest that orexin-A and glucose effects on the PVN stimulate gastric acid secretion. This stimulatory effect is probably mediated by orexin-1 receptors.

Prevalence of type 2 diabetes in the Islamic Republic of Iran: systematic review and meta-analysis.

We estimated the prevalence of type 2 diabetes in the Islamic Republic of Iran by systematic review of all available studies in the country between 1996 and 2004 and aggregation of the data using meta-analysis and meta-regression methods. In those > 40 years the prevalence was 24% and it increased by 0.4% with each year after 20 years of age. The risk of type 2 diabetes was 1.7% greater in women than men (P < 0.001). The prevalence of type 2 diabetes appears higher in the Islamic Republic of Iran than in other developing countries but because of differences in age pyramids, the crude prevalence is not an appropriate indicator and age-adjusted or age-specific prevalences should be used.

Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast.

Idiopathic Pulmonary Fibrosis (IPF) is characterized by injury and loss of lung epithelial cells, accumulation of fibroblasts/myofibroblasts and abnormal remodeling of the lung parenchyma. The prognosis for IPF patients is poor and current therapies are largely ineffective in preventing respiratory failure. Current therapeutic approaches target epithelial cell replacement, manipulation of fibroblasts/myofibroblasts, modulation of procoagulant/fibrinolytic activities, cytokine and growth factor production, angiogenesis, and reduction of oxidative stress. Myofibroblasts are the primary effector cells in fibrosis. These cells may be derived by the activation and proliferation of resident lung fibroblasts, from epithelial-mesenchymal transition (EMT), or through recruitment of circulating fibrocytes. Transforming growth factor beta (TGFbeta) is a profibrotic factor that increases fibroblast proliferation, stimulates the synthesis and deposition of connective tissue, and inhibits connective tissue breakdown. TGFbeta acts through the promoter of the type 1 collagen gene causing increased collagen synthesis. In addition, TGFbeta induces EMT in alveolar epithelial cells (AECs) in vitro and in vivo. AECs exhibit substantial plasticity and may serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. Therapeutic interventions interfering with the pathways that lead to myofibroblast expansion and AEC apoptosis should be of considerable benefit in the treatment of IPF. This review will focus on the critical role of TGFbeta on AECs EMT and myofibroblasts in the development of fibrosis.

An essential role for CCAAT/enhancer binding protein beta in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) was found to be a key regulator of myofibroblast differentiation in vitro, and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBPbeta in the development of pulmonary fibrosis, experiments using C/EBPbeta null mice and their wild-type littermates were conducted. Our findings indicated that, compared to wild-type mice, animals deficient in C/EBPbeta showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBPbeta regulates fibrosis indicated that knockout of C/EBPbeta attenuates inflammatory cytokine expression in bleomycin-treated mice. The reduced alpha-smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline-treated C/EBPbeta deficient mice suggests that C/EBPbeta regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBPbeta deficient mice exhibited higher proliferative rates than those from wild-type mice. These data suggest that C/EBPbeta plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation.

Role of Eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis.

Eotaxin-1/CCL11 and its receptor CCR3 are involved in recruitment of eosinophils to diverse tissues, but their role in eosinophil recruitment in pulmonary fibrosis is unclear. The present study examined the pulmonary expression of CCL11 and CCR3 during bleomycin (blm)-induced lung injury and determined their importance in the recruitment of inflammatory cells and the development of lung fibrosis. In mice, blm induced a marked pulmonary expression of CCL11 and CCR3. Immunostaining for CCR3 revealed that this receptor was not only expressed by eosinophils but also by neutrophils. CCL11-deficient (CCL11(-/-)) mice developed significantly reduced pulmonary fibrosis. Expression of profibrotic cytokines such as transforming growth factor-beta1 was diminished in the absence of CCL11. Furthermore, increased lung expression of CCL11 significantly enhanced blm-induced lung fibrosis and production of profibrotic cytokines. These effects were also associated with an increase of eosinophil and neutrophil pulmonary infiltration. In contrast, mice treated with neutralizing CCR3 antibodies developed significantly reduced pulmonary fibrosis, eosinophilia, neutrophilia, and expression of profibrotic cytokines. Together, these data suggest that CCL11 and CCR3 are important in the pulmonary recruitment of granulocytes and play significant pathogenic roles in blm-induced lung fibrosis.

Molecular mechanisms of and possible treatment strategies for idiopathic pulmonary fibrosis.

Pulmonary fibrosis is characterized by lung inflammation and abnormal tissue repair, resulting in the replacement of normal functional tissue with an abnormal accumulation of fibroblasts and deposition of collagen in the lung. This process involves cellular interactions via a complex cytokine-signaling mechanism and heightened collagen gene expression, ultimately resulting in its abnormal collagen deposition in the lung. Our current understanding of the pathogenesis of pulmonary fibrosis suggests that in addition to inflammatory cells, the fibroblast and signaling events that mediate fibroblast proliferation and myofibroblasts, play important roles in the diverse processes that constitute fibrosis. Increasing knowledge of cytokine biology, cytokine-signaling and cell matrix interactions have shed some light on the genesis of pulmonary fibrosis; however, the importance of inflammation in pulmonary fibrosis remains controversial. This remains true because the inflammatory component is variable at the time of diagnosis, and the most potent anti-inflammatory drugs that have been widely used in the treatment of pulmonary fibrosis do not seem to interfere with the fibrotic disease progression. Pulmonary fibrosis is a highly lethal disorder, which continues to pose major clinical challenges because an effective therapeutic regimen is yet to be determined. This review summarizes recent progress in understanding the molecular mechanisms of pulmonary fibrosis, and includes a more detailed discussion of the potential points of therapeutic attack in pulmonary fibrosis. In addition, a detailed discussion is presented regarding each of the potential therapies which have emerged from the animal models of pulmonary fibrosis, and which have been developed through advances in cellular and molecular biology.

Oryzalin-induced chromosome doubling in Rosa and its effect on plant morphology and pollen viability.

Shoot tips of the diploid rose Thérèse Bugnet were treated in vitro to oryzalin at concentrations of 5 and 15 microM. Tetraploid shoots were obtained in highest frequencies (40%) after exposure to 5 microM oryzalin for 14 days. Thin (1 mm) nodal sections were treated with 5 microM oryzalin and the highest frequency of tetraploids (66%) was obtained after exposure for only 1 day. The shorter exposure times required to induce chromosome doubling in thin nodal sections is attributed to the more efficient delivery of oryzalin to the meristem. Tetraploids were obtained from four diploid roses and hexaploids from two triploid roses. Chromosome doubling was accompanied by increases in thickness and a darker green colouration of the leaves and, in all diploid to tetraploid and one triploid to hexaploid conversion, the breadth/length ratio of leaflets was significantly increased. Internodes were longer in tetraploids than diploids but significantly shorter in hexaploids than triploids. The number of petals per flower in the tetraploid form of Thérèse Bugnet was double that of the diploid. Significant increases in pollen viability accompanied chromosome doubling of all four diploids and one of the two triploids.

Lung interleukin-4 gene expression in a murine model of bleomycin-induced pulmonary fibrosis.

Interleukin-4 (IL-4) is known to activate mononuclear cells as well as fibroblasts, all of which are important in the pathogenesis of pulmonary fibrosis. To investigate the potential role of this cytokine, lung IL-4 expression was examined in a murine model of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced in CBA/J mice by endotracheal injection of bleomycin on day 0. On selected days after treatment, lungs were harvested for reverse transcriptase polymerase chain reaction (RT-PCR), Northern, in-situ hybridization and immunohistochemical analyses. RT-PCR and Northern analyses revealed significant increases in lung IL-4 mRNA content between days 3 and 14 after induction of lung injury, which decreased toward control level after day 21. Both in-situ hybridization and immunohistochemistry showed low or undetectable IL-4 expression in control lungs and in injured lungs before day 3 after bleomycin injection. There was however elevated expression in mononuclear cells and macrophages between days 3 and 14, localized to areas of active fibrosis. These results demonstrate that IL-4 is upregulated significantly in this model. They suggest a potential role for this cytokine in pulmonary fibrosis, perhaps via its ability to stimulate and amplify the inflammatory response, stimulate collagen synthesis in fibroblasts, and thus promote the progression to fibrosis and end stage lung disease.

Role of cytokines and cytokine therapy in wound healing and fibrotic diseases.

Cytokines are critical to a myriad of fundamental homeostatic and pathophysiological processes such as fever, wound healing, inflammation, tissue repair and fibrosis. They play important roles in regulating cell function such as proliferation, migration, and matrix synthesis. It is the balance or the net effect of the complex interplay between these mediators, which appears to play a major role in regulating the initiation, progression and resolution of wounds. Wound healing involves a complex process including induction of acute inflammation by the initial injury, followed by parenchymal and mesenchymal cell proliferation, migration, and activation with production and deposition of extracellular matrix. Failure to resolve or abnormal wound healing results in fibrosis. The latter process involves similar cellular interactions via complex cytokine networks, which result in extensive remodeling with heightened extracellular matrix production and their abnormal deposition in the tissue. Various cytokines, both promoting and inhibiting fibrogenesis, have been implicated in the pathogenesis of fibrosis and wound healing. Recent progress in understanding the mechanisms underlying the pathogenesis of fibrosis leads us to expect that inhibitors of pro-fibrogenic cytokines and growth factors may be useful as novel therapeutic agents in controlling undesirable fibrosis. In this review, the role of cytokines in wound healing and fibrosis will be summarized and highlighted with more detailed discussion reserved for the possible points of therapeutic attack in pulmonary fibrosis. In this review, the major cytokines that are in current clinical use will be also discussed. In addition, advances in the application of novel cytokines and anti-cytokines for accelerating wound healing and attenuating fibrosis both at the experimental and the clinical trial levels will be discussed.

Induction of telomerase activity in fibroblasts from bleomycin-injured lungs.

Bleomycin-induced lung injury causes increased fibroblast numbers in the lung and pulmonary fibrosis. Studies of fibroblasts isolated from such injured lungs have revealed evidence of increased intrinsic proliferative capacity, but the mechanism is unknown. Telomerase catalyzes the addition of telomeric DNA repeats onto chromosomal ends, which is associated with increased cellular life span or immortality. To examine whether telomerase might play a role in regulating fibroblast proliferative capacity in pulmonary fibrosis, lung fibroblasts were isolated from rats treated with endotracheal injections of phosphate-buffered saline or bleomycin. At selected time points, the rats were killed and lung fibroblasts isolated. The isolated cells and lung tissue were then used in experiments for measurement of telomerase activity. The results show undetectable telomerase activity in fibroblasts isolated from control uninjured lungs, or in the control lung tissue extracts. Similar results were obtained in cells and lung tissue from Days 1, 3, and 28 bleomycin-injured lungs. However, significant telomerase activity was detected in fibroblasts and tissue extracts isolated from Days 7, 14, and 21 bleomycin-treated rat lungs, with maximal activity observed in the Day 14 samples. Analysis of the isolated cells for telomerase messenger RNA or reverse transcriptase expression, combined with alpha-smooth-muscle actin expression by immunohistochemistry, revealed that telomerase expression localized primarily to nonmyofibroblasts. These findings suggest that in addition to elevated growth factor expression, the injured lung fibroblast population may contain cells with increased life span, which could contribute to the observed overall increase in lung fibroblast numbers.

Underutilization and clinical benefits of angiotensin-converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction.

Despite evidence of therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors for congestive heart failure and asymptomatic left ventricular (LV) dysfunction, recent studies suggest that in heart failure patients, rates of ACE inhibitor usage in clinical practice remain low. In this study, the medical records of 107 patients with documented LV dysfunction were investigated for patterns of ACE inhibitor usage; 6-month and 1-year outcomes and event rates were evaluated. At index admission, 48% patients did not receive ACE inhibitor treatment, 32% were initiated on treatment, 19% continued on a prior regimen, and 1% were discontinued. Patients seen by a cardiologist were more likely to receive ACE inhibitor treatment (53% vs 35%, p = 0. 172), as were patients with histories of hypertension (60% vs 40%, p = 0.044) or myocardial infarction (56% vs 44%, p = 0.221). Significantly shorter hospitalizations (5.9 vs 9.5 days, p = 0.001) were noted for patients with on-going ACE inhibitor treatment compared with those receiving newly initiated treatment or no treatment. At time of hospital discharge, 102 patients were alive. Of 54 patients who received ACE inhibitors, 67% received an insufficient dose. At a 6-month follow-up, of 51 patients on ACE inhibitors, 23% died or were readmitted to hospital compared with 55% of nonusers (p = 0.001). At 1 year, this event rate was 31% among ACE inhibitor users versus 71% among nonusers (p < 0.0001). Bivariate and multivariate analysis revealed absence of ACE inhibitor use as the only significant variable associated with the event rate (p < 0.0011). Thus, about half of patients with asymptomatic LV dysfunction received ACE inhibitors; 2/3 of these did not receive a sufficient dose. ACE inhibitor usage increased with involvement of a cardiologist, presence of coexistent hypertension, or prior myocardial infarction. Ongoing ACE inhibitor therapy was associated with shorter hospitalizations and fewer hospital readmissions or deaths.

Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin.

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.

Immunological properties of plaque purified strains of live attenuated respiratory syncytial virus (RSV) for human vaccine.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in infants, young children, and the elderly. Efforts to develop satisfactory live or inactivated vaccines have not yet been proven successful. Our research focuses on the development of four purified live attenuated RSV sub-type A human vaccine clones. Temperature sensitive (ts) and attenuated purified clones of either cold-adapted (ca) RSV or high-passage (hp) RSV were administered intra-nasally (i.n.) to BALB/c mice and tested for immunogenicity. All four clones produced significant anti-RSV F IgG2a and IgG1 titres in the sera of mice, RSV-specific neutralizing titres higher than those produced by their wild-type progenitor viruses, cytotoxic T-lymphocyte (CTL) activity, and total protection against wild-type (wt) viral challenge. These purified vaccine candidates await testing in humans to determine which contain the required balance between immunogenicity and attenuation.