Bone Marrow Adiposity in Premenopausal Women With Type 2 Diabetes With Observations on Peri-Trabecular Adipocytes.

CONTEXT: No study has yet evaluated the relationships among bone marrow adiposity (BMA), bone histomorphometry (BH), and glycemic control in premenopausal women with type 2 diabetes (T2DM). OBJECTIVE: We aimed to assess the effect of glycemic control on BMA, correlate the parameters of BH with BMA, and correlate BMA with the use of hypoglycemic agents and with bone mineral density (BMD). METHODS: This was a cross-sectional study that evaluated 26 premenopausal women with T2DM who were divided into groups with HbA1c < 7% (good control [GC], n = 10) and HbA1c > 7% (poor control [PC], n = 16). BMA parameters (adipocyte number [Ad.N], total adipocyte perimeter [Ad.Pm], total adipocyte area [Ad.Ar], percentage adipocyte volume per marrow volume [Ad.V/Ma.V]) and peri-trabecular adipocyte number divided by bone surface (Ad.N/BS) were evaluated. BH static (bone volume fraction [BV/TV], osteoid thickness [O.Th], osteoid surface/bone surface [OS/BS]) and dynamic parameters and serum insulin-like growth factor-1 were measured. BMA data were compared between the GC and PC groups. Correlations were performed. RESULTS: Ad.N, Ad.Pm, and Ad.Ar were higher in PC (all, P = 0.04). HbA1c correlated positively with Ad.N/BS (P < 0.01) and Ad.N/BS correlated negatively with O.Th (P < 0.01) and OS/BS (P = 0.02). Positive and negative correlations were observed between insulin and metformin use, respectively, with all adipocyte parameters except Ad.N/BS (P < 0.05). Structural parameters were negatively correlated with the BMA. BMD of the femoral neck (r = -549, P < 0.01) and total femur (r = -0.502, P < 0.01) were negatively correlated with Ad.V/Ma.V. CONCLUSION: Poor glycemic control is associated with hyperplasia and hypertrophy of BMAs and with lower BV/TV. Ad.N/BS, a new BMA parameter, is correlated with HbA1c and negatively with O.Th. The use of insulin seems to stimulate the expansion of BMA while that of metformin has the opposite effect. These findings suggest that the increase in BMA may play a role in the T2DM bone disease; on the other hand, good glycemic control might help prevent it.

A influência do oxido nítrico na fisiopatologia da neuropatia glaucomatosa / The influence of nitric oxide on the pathophysiology of glaucomatous neuropathy

Resumo O oxido nitrico (NO) é um fator relaxante derivado do endotélio e um potente vasodilatador que impacta em vários sistemas em todo o corpo. Estudos comprovam que o fluxo sanguíneo ocular basal é regulado pelo NO, sendo um importante regulador da homeostase, especialmente dentro dos tecidos uveais. A disfunção da produção de NO seria associado ao glaucoma através da alteração da perfusão da cabeça do nervo óptico associado ao aumento da pressão intraocular devido um sistema de drenagem trabecular deficiente. O NO tornou-se uma molécula atraente para o tratamento do glaucoma devido a possibilidade de modulação da drenagem trabecular, abaixando a pressão intraocular e ação neuroprotetora melhorando a perfusão sanguínea na cabeça do nervo óptico.

Abstract Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve.

Vesicular stomatitis virus glycoprotein- and Venezuelan equine encephalitis virus-derived glycoprotein-pseudotyped lentivirus vectors differentially transduce corneal endothelium, trabecular meshwork, and human photoreceptors.

The ability to deliver a large transgene efficiently to photoreceptors using viral vectors remains problematic and yet is critical for the future therapy of inherited retinal diseases such as Stargardt's and Usher's 1B. Herein, we examine the ocular tropism of a HIV-1-based lentivirus vector pseudotyped with Venezuelan equine encephalitis virus-derived glycoprotein (VEEV-G) after intraocular delivery to the posterior and anterior chambers of C57BL/6 wild-type mice. Reporter gene (EGFP) expression was evaluated using in vivo fluorescence imaging followed by postmortem immunohistochemistry and retinal function assessed by electroretinography. Intracameral administration of VEEV-G and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped vectors resulted in robust transgene expression in the corneal endothelium and trabecular meshwork. After subretinal administration, onset of transgene expression was observed in the retinal pigment epithelium (RPE) 1 day postinjection with both VEEV-G and control VSV-G pseudotypes, but no significant photoreceptor transduction was apparent. Substantial degeneration of the outer nuclear layer was observed with VEEV-G-pseudotyped vector, which corresponded to ablation of retinal function. Subretinal administration of VSV-G was observed to result in significant suppression of electrophysiological function compared with buffer-injected and uninjected control eyes. Suppression of the c-wave amplitude, in addition to reduced RPE65 expression, indicated potential RPE dysfunction. Ex vivo tropism of VSV-G was assessed using organotypic culture of explanted retina harvested from wild-type mice and human patients undergoing retinal detachment surgery to examine the prevention of transduction by physical barriers and species differences in tropism.

Synthesis and secretion of transferrin by a bovine trabecular meshwork cell line

The trabecular meshwork (TM) is the main outflow pathway in the mammalian eye. Oxidative damage to TM cells has been suggested to be an important cause of impairment of TM functions, leading to deficient drainage of aqueous humor, with deleterious consequences to the eye. Transferrin, a metalloprotein involved in iron transport, has been characterized as an intrinsic eye protein. Since transferrin is implicated in the control of oxidative stress, the objective of the present study was to determine if a bovine TM cell line (CTOB) synthesizes and secretes transferrin. The CTOB cell line was cultured in the presence of 35S-methionine and the incubation medium was submitted to immunoprecipitation. Total RNAs from CTOB and isolated bovine TM (freshly isolated, incubated or not) were subjected to the reverse transcription-polymerase chain reaction and the amplification products were sequenced. Also, both CTOB and histological TM preparations were processed for transferrin immunolocalization. A labeled peptide of about 80 kDa, the expected size for transferrin, was immunopurified from CTOB samples obtained from the incubation assays. The reverse transcription-polymerase chain reaction and sequencing experiments detected the presence of transferrin mRNA in CTOB and isolated bovine TM. Reactivity to antibodies against transferrin was observed both in CTOB and TM. The results obtained in all of these experiments indicated that the TM is capable of synthesizing and secreting transferrin. The possible implications for the physiology of the eye are discussed.

Synthesis and secretion of transferrin by a bovine trabecular meshwork cell line.

The trabecular meshwork (TM) is the main outflow pathway in the mammalian eye. Oxidative damage to TM cells has been suggested to be an important cause of impairment of TM functions, leading to deficient drainage of aqueous humor, with deleterious consequences to the eye. Transferrin, a metalloprotein involved in iron transport, has been characterized as an intrinsic eye protein. Since transferrin is implicated in the control of oxidative stress, the objective of the present study was to determine if a bovine TM cell line (CTOB) synthesizes and secretes transferrin. The CTOB cell line was cultured in the presence of 35S-methionine and the incubation medium was submitted to immunoprecipitation. Total RNAs from CTOB and isolated bovine TM (freshly isolated, incubated or not) were subjected to the reverse transcription-polymerase chain reaction and the amplification products were sequenced. Also, both CTOB and histological TM preparations were processed for transferrin immunolocalization. A labeled peptide of about 80 kDa, the expected size for transferrin, was immunopurified from CTOB samples obtained from the incubation assays. The reverse transcription-polymerase chain reaction and sequencing experiments detected the presence of transferrin mRNA in CTOB and isolated bovine TM. Reactivity to antibodies against transferrin was observed both in CTOB and TM. The results obtained in all of these experiments indicated that the TM is capable of synthesizing and secreting transferrin. The possible implications for the physiology of the eye are discussed.