What is the role of imaging in acute low back pain?

In patients with non specific acute low back pain, without the red flags, a conservative approach is preferable, with assessment in 4-6 weeks. The natural history of low back pain is favorable with improvement over time, thus reassurance to such patients is very important. However, a plain radiograph or more advanced imaging techniques like MRI/CT may be ordered in back pain associated with radiculopathy or spinal stenosis and back pain associated with progressive neurologic deficits. There is limited role of imaging in non specific acute low back pain without the red flags, as the findings correlate poorly with symptoms.

Pretreatment of diabetic rats with lipoic acid improves healing of subsequently-induced abrasion wounds.

The etiology of delayed or impaired wound-healing in diabetic individuals is multifactoral, but peripheral vascular dysfunction is an underlying factor in the majority of cases. Recent studies have shown that lipoic acid improves vascular function in diabetic skin and reduces the symptoms associated with the diabetic peripheral neuropathy. In this study, rats were made diabetic with streptozotocin (STZ) and treated systemically on alternative days with lipoic acid (100 mg/kg given via intraperitoneal injection) for 8 weeks. Untreated STZ-diabetic rats and non-diabetic rats served as control. At the end of the 8-week period, rats from all the three groups were subjected to abrasion wound formation. Skin wounds healed more rapidly in untreated non-diabetic rats than in the untreated diabetic rats. Wounds in lipoic acid-treated diabetic rats healed more rapidly than wounds in untreated diabetic rats. Subsequent in vitro studies demonstrated that lipoic acid protected endothelial cells from oxidant injury. At the same time, lipoic acid had no apparent effect on endothelial cell proliferation and had no measurable effect on fibroblast function (proliferation, collagen synthesis and matrix metalloproteinase expression). These findings suggest that prophylactic use of lipoic acid might be useful in preventing the development of non-healing skin ulcers from minor traumas in at-risk skin.

Topical pretreatment of diabetic rats with all-trans retinoic acid improves healing of subsequently induced abrasion wounds.

In the current study, rats were made diabetic with streptozotocin (STZ) and maintained for 8 weeks, during which time they were treated topically on alternative days with a solution of 0.1% all-trans retinoic acid in a vehicle of 70:30% ethanol/propylene glycol. STZ-induced diabetic rats treated with vehicle served as controls. Additional nondiabetic rats were treated with all-trans retinoic acid or vehicle in parallel. At the end of the 8-week period, rats from all four treatment groups were subjected to abrasion wound formation. Wounds healed more rapidly in vehicle-treated nondiabetic skin than in vehicle-treated diabetic skin (96% of the wound surface area closed in nondiabetic rats within 6 days vs. 41% closed in diabetic rats). Wounds in all-trans retinoic acid-treated diabetic skin healed more rapidly than wounds in vehicle-treated diabetic skin (85% of the wound surface area closed in all-trans retinoic acid-treated diabetic rats vs. 41% closed in vehicle-treated diabetic rats). At the histological level, recently healed skin from vehicle-treated diabetic rats was shown to contain a thin, wispy provisional matrix in which many of the embedded cells were rounded and some were pycnotic. In contrast, a much denser provisional matrix with large numbers of embedded spindle-shaped cells was observed in healed wounds from diabetic skin that had been pretreated with all-trans retinoic acid. The all-trans retinoic acid-treated diabetic skin was histologically similar to vehicle-treated (or all-trans retinoic acid-treated) skin from nondiabetic animals. In light of these findings, we suggest that prophylactic use of retinoid-containing preparations might be useful in preventing the development of nonhealing skin ulcers resultant from minor traumas in at-risk skin.

PADMA 28: a multi-component herbal preparation with retinoid-like dermal activity but without epidermal effects.

PADMA 28, a multi-component herbal mixture formulated according to an ancient Tibetan recipe, was assessed for effects on human dermal fibroblasts and epidermal keratinocytes in monolayer culture, and for effects on human skin in organ culture. PADMA 28 stimulated survival of fibroblasts in monolayer culture. In fibroblast monolayer culture and human skin organ culture, levels of matrix metalloproteinase-1 (MMP-1; interstitial collagenase) were reduced and type I procollagen production was increased. When keratinocytes were examined, there was no evidence of growth stimulation over a wide range of PADMA 28 concentrations. At high concentration, PADMA 28 inhibited keratinocyte proliferation. When organ cultures of human skin were treated with PADMA 28, there was no evidence of hyperplastic growth in the epidermis. Topical treatment of rhino mice with PADMA 28 failed to induce epidermal hyperplasia and was completely non-irritating. The ability to stimulate collagen production and inhibit the major collagen-degrading enzyme in skin without inducing a hyperplastic response in the epidermis may provide a basis for development of the herbal preparation as a "skin-repair" agent.

Retinoid-induced epidermal hyperplasia in human skin organ culture: inhibition with soy extract and soy isoflavones.

Organ cultures of human skin were incubated for 8 days with 1 microg/ml 14-all trans retinoic acid (14-all trans RA) and concomitantly treated with varying concentrations of soy extract. The epidermis of organ cultures treated with 14-all trans RA alone underwent a hyperplastic response. In cultures treated with a combination of 14-all trans RA and soy extract (4-40 microg/ml), hyperplasia was reduced by 16-41%. The same concentrations of soy extract that reduced epidermal hyperplasia in organ culture also suppressed proliferation of rapidly growing keratinocytes in monolayer culture (approximately 25% reduction at 20 and 40 microg/ml). On the other hand, soy extract did not further inhibit proliferation of quiescent keratinocytes; rather, it stimulated growth (50-52% increase relative to control). When dermal fibroblasts were examined for a response to soy extract (i.e., proliferation and synthesis of type I procollagen), both responses were stimulated (proliferation: 75% increase and collagen production 114% increase relative to control). Genistein, the major isoflavone in extracts of soy also inhibited epidermal hyperplasia in organ culture (34-40% reduction relative to control). The same concentrations that reduced epidermal hyperplasia (0.5-1.0 microg/ml) also inhibited keratinocyte proliferation in monolayer culture but had little effect on fibroblast growth. Two other isoflavones (daidzein and glycetein) were also inhibitory, but were less effective than genistein. Taken together, these data suggest that use of soy extract or its constituent isoflavones in conjunction with 14-all trans RA may provide a way to mitigate unwanted epidermal effects of topical retinoid therapy without compromising beneficial retinoid effects in the dermis.

All-trans-retinoic acid suppresses matrix metalloproteinase activity and increases collagen synthesis in diabetic human skin in organ culture.

Diabetes increases susceptibility to chronic skin ulceration. The etiology of chronic wound formation in diabetic individuals is multifactoral but may be accelerated by changes in the structure and function of the skin secondary to impaired fibroblast proliferation, decreased collagen synthesis, and increased matrix metalloproteinase (MMP) expression. This study explored the effects of all-trans-retinoic acid (RA) on cellular and biochemical features of diabetic human skin in organ culture. Two-mm skin biopsies from hip or ankle were obtained from diabetic subjects and incubated for 9 days in the absence or presence of 2 micro mol/L RA. Hip skin from non-diabetic individuals served as control. Following organ culture incubation, untreated and RA-treated tissue was examined histologically after staining with hematoxylin and eosin. In parallel, organ culture-conditioned medium collected on days 5 and 7 was assayed for levels of active and total MMP-1 (interstitial collagenase) and MMP-9 (gelatinase B). The same organ culture fluids were assayed for the presence of soluble collagen. In comparison with skin from non-diabetic individuals, diabetic skin demonstrated no major differences in overall epidermal thickness or collagen production (both were increased in RA-treated tissue as compared to non-RA-treated tissue). In contrast, levels of MMP-9 (active forms) were elevated in organ culture fluid from diabetic skin as compared to non-diabetic control skin. In the presence of RA, active forms of both MMP-1 and MMP-9 were reduced. Together, these data suggest that RA has the capacity to improve structure and function of diabetic skin, and that a major effect is on reduction of collagen-degrading MMPs.

Matrix metalloproteinases in acute inflammation: induction of MMP-3 and MMP-9 in fibroblasts and epithelial cells following exposure to pro-inflammatory mediators in vitro.

Recent studies have demonstrated important pro-inflammatory roles for two matrix metalloproteinases (MMPs)-MMP-3 (stromelysin-1) and MMP-9 (gelatinase B)-in acute lung injury [Am. J. Respir. Cell Mol. Biol. 24 (2001) 1]. A role for MMP-3 in skin inflammation has also been demonstrated [Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 6885]. While leukocytes (neutrophils and macrophages) are known to elaborate these tissue-destructive enzymes, parenchymal cells are also capable of synthesizing MMPs. In the present study, we examined the production of MMP-3 and MMP-9 by rodent lung fibroblasts, type II epithelial cells, and vascular endothelial cells. Dermal fibroblasts were also examined. Cells were examined under control conditions and in response to agonists that induce acute inflammatory tissue injury (IgG-containing immune complexes and lipopolysaccharide [LPS]). In the absence of stimulation, MMP-3 and MMP-9 were not detected or were present at low level. However, upon stimulation with either of the two pro-inflammatory agonists, production of both enzymes occurred in fibroblasts and epithelial cells (though not in endothelial cells). The observation that resident cells in the tissue parenchyma can elaborate MMPs in direct response to pro-inflammatory stimuli provides insight into possible mechanisms by which tissue damage occurs in acute inflammation.