Osteoblast activity is diminished in young Spontaneously Hypertensive Rats

Spontaneously Hypertensive Rats (SHR) are used as a genetic model of essential hypertension. Reductions in cortical and cancellous bone mass and increased bone turnover have been observed in aged SHR vs. Wistar-Kyoto (WKY) rats, normotensive genetics controls. In addition, antihypertensive aids have been effective in improving bone parameters in hypertensive rats. Thus, the relation between hypertension and bone remodeling warrants further attention. The purpose of this study was to determine how acute (i.e., 9 weeks) hypertension effects bone remodeling parameters (i.e., osteoclast and osteoblast activity). Methods: Right femora from 14-week-old SHR (n=5) and WKY (n=4) rats were dissected, fixed in 10% formalin and processed for bone histomorphometry for the examination of bone microarchitectural (bone volume/total volume ratio [BV/TV, %], trabecular thickness [Tb.Th, μm], trabecular number [Tb.N /mm] and trabecular separation [Tb. Sp, μm]) and bone static (osteoid surface/bone surface [OS/BS, %], osteoblast surface/bone surface [Ob.S/BS, %], number of osteoblast per total area [N.Ob/T.Ar], osteoclast surface/bone surface [Oc.S/BS, %)], and number of osteoclast per total area [N.Oc/T.Ar]) properties. Results: Body mass did not differ between SHR and WKY rats (i.e., 357 ± 6g vs. 351 ± 8g). No significant differences in bone microarchitectural properties (i.e., BV/TV, Tb.Th, Tb.N and Tb.Sp) were observed after acute hypertension. However, OS/BS, which represents newly formed yet unmineralized bone tissue, was significantly (p \u3c 0.05) reduced in SHR vs. WKY rats. In addition, osteoblast activity (Ob.S/BS) was significantly (p \u3c 0.05) diminished with hypertension. Further, there was a tendency (p = 0.08) for higher N.Oc/T.Ar in SHR vs. WKY rats. Conclusions: Results from this study indicate that hypertension alters bone remodeling parameters by decreasing osteoblast and increasing osteoclast activity. Differences in bone mircoarchitectural properties (i.e., BV/TV, Tb.Th, Tb.N and Tb.Sp) were not observed at this age; however, the alterations in bone cellular activity (i.e., OS/BS, Ob.S/BS and N.Oc/T.Ar) imply that reductions in bone mass are inevitable as the duration of hypertension increases

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice

AIMS: Hutchinson-Gilford progeria syndrome (HGPS) is an accelerated ageing syndrome associated with premature vascular disease and death due to heart attack and stroke. In HGPS a mutation in lamin A (progerin) alters nuclear morphology and gene expression. Current therapy increases the lifespan of these children only modestly. Thus, greater understanding of the underlying mechanisms of HGPS is required to improve therapy. Endothelial cells (ECs) differentiated from induced pluripotent stem cells (iPSCs) derived from these patients exhibit hallmarks of senescence including replication arrest, increased expression of inflammatory markers, DNA damage, and telomere erosion. We hypothesized that correction of shortened telomeres may reverse these measures of vascular ageing. METHODS AND RESULTS: We generated ECs from iPSCs belonging to children with HGPS and their unaffected parents. Telomerase mRNA (hTERT) was used to treat HGPS ECs. Endothelial morphology and functions were assessed, as well as proteomic and transcriptional profiles with attention to inflammatory markers, DNA damage, and EC identity genes. In a mouse model of HGPS, we assessed the effects of lentiviral transfection of mTERT on measures of senescence, focusing on the EC phenotype in various organs. hTERT treatment of human HGPS ECs improved replicative capacity; restored endothelial functions such as nitric oxide generation, acetylated low-density lipoprotein uptake and angiogenesis; and reduced the elaboration of inflammatory cytokines. In addition, hTERT treatment improved cellular and nuclear morphology, in association with a normalization of the transcriptional profile, effects that may be mediated in part by a reduction in progerin expression and an increase in sirtuin 1 (SIRT1). Progeria mice treated with mTERT lentivirus manifested similar improvements, with a reduction in inflammatory and DNA damage markers and increased SIRT1 in their vasculature and other organs. Furthermore, mTERT therapy increased the lifespan of HGPS mice. CONCLUSION: Vascular rejuvenation using telomerase mRNA is a promising approach for progeria and other age-related diseases

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Mullein survey and removal efforts on Mauna Loa in Hawai'i Volcanoes National Park

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.Common mullein (Verbascum thapsus L.) is a biennial herb naturalized in mostly temperate areas on the Island of Hawai’i. Mullein was first observed growing on Mauna Loa in Hawai’i Volcanoes National Park in the 1970’s. Localized efforts to eradicate mullein along roadsides in the Park began in 1989. This report documents monitoring and control efforts of mullein in the Park between 1994-1 999. Mullein occupies 1,003 hectares of open lava flows located between 1,500 and 2,100 m elevation in the Park. Range expansion is expected to continue at both lower and higher elevations. Densities and recruitment are highest (>1,400 ind/ha) on weathered ‘a’a flows that edge vegetated kipukas. Lowest densities (<1 ind/ha) and recruitment occur on open ‘a’a with little or no soil development. Recruitment of new individuals is highly variably between years and is likely influenced by fluctuations in seasonal rainfall. Manual uprooting mullein effectively reduces populations by the third or fourth year of annual removal treatments. Successful control requires consistent and thorough follow-up treatment. Workloads vary between 5-10 ha/worker days in moderate to low density infested areas. An estimated 200 worker days will be required annually to remove mullein from existing populations, other than the most densely infested areas in the Park. Based on these findings, management should emphasize containment and range reduction of the current distribution. Cooperative agreements with private and state landowners should be made to control mullein in areas adjacent to the Park in order to reduce re-invasion from outside areas into the Park. Use of herbicides and biological control agents as alternatives to uprooting mullein should be investigated. Long term studies of the impact of mullein on native plant communities will help managers prioritize mullein control efforts in the Park.National Park Service Cooperative Agreement CA 8000 2 900

Vegetation Maps at the Passage of the Taylor Grazing Act (1934): A Baseline to Evaluate Rangeland Change After a Regime Shift

The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform March 202

Rare Histological Variants of Liver Cancer and Their Management: A Single-Institution Experience

Primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma, are a major cause of cancer-related morbidity and mortality worldwide. There are several histologically and biologically distinct subtypes of liver cancer that have previously been reported. However, literature regarding the nonsurgical management of these patients upon disease recurrence remains limited. These variants include combined HCC-cholangiocarcinoma (cHCC-CC), Epstein–Barr virus- (EBV-) associated carcinoma, undifferentiated carcinoma, and clear cell or thyroid-like variants of HCC. Here, we aim to highlight the pathologic features, clinical course, and outcomes of five patients with these unusual hepatic tumors and explain the rationale behind the choice of their systemic therapies upon disease recurrence. All patients underwent surgical resection as the standard of care for localized disease, and upon relapse, they were treated with either chemotherapy, targeted therapy, immunotherapy, or active surveillance based on the clinical context and tumor histology. These rare variants are important to recognize as they have prognostic and therapeutic implications, and there are currently insufficient data in the literature to guide further therapy