Biomedical subjects

Michael S Kolodney

Publications and source records attributed to Michael S Kolodney.

9 recordsLinked to original sources

PubMed2006

Mesotherapy and phosphatidylcholine injections: historical clarification and review.

BACKGROUND: Mesotherapy was originally conceived in Europe as a method of utilizing cutaneous injections containing a mixture of compounds for the treatment of local medical and cosmetic conditions. Although mesotherapy was traditionally employed for pain relief, its cosmetic applications, particularly fat and cellulite removal, have recently received attention in the United States. Another treatment for localized fat reduction, which was popularized in Brazil and uses injections of phosphatidylcholine, has been erroneously considered synonymous with mesotherapy. Despite their attraction as purported "fat-dissolving" injections, the safety and efficacy of these novel cosmetic treatments remain ambiguous to most patients and physicians. OBJECTIVE: To distinguish mesotherapy from phosphatidylcholine injections by reviewing their history and the relevant experimental or clinical findings. METHODS: A comprehensive search of Medline indexed literature and conference proceedings. RESULTS: All the published studies evaluating the clinical efficacy of traditional mesotherapy currently originate from Europe. These reports focus primarily on musculoskeletal pain and vascular disease, rather than cosmetic applications. Although experimental data suggest that a number of traditional mesotherapy ingredients may theoretically reduce fat, these effects have not been supported in peer-reviewed studies. An increasing number of reports demonstrate that subcutaneous injections of a formula containing phosphatidylcholine combined with its emulsifier, deoxycholate, are effective in removing small collections of adipose tissue. Cell lysis, resulting from the detergent action of deoxycholate, may account for this clinical effect. CONCLUSIONS: Mesotherapy is distinct from a method of treating adipose tissue with subcutaneous injections of deoxycholate alone or in combination with phosphatidylcholine. Additional clinical and experimental studies are necessary to more definitively establish the safety and efficacy of these treatments.

Adipose Tissue↗

PubMed2005

Lipomas treated with subcutaneous deoxycholate injections.

BACKGROUND: Lipomas are benign neoplasms of mature fat cells. Current treatments are invasive and carry the risk of scarring. Injections of phosphatidylcholine solubilized with deoxycholate, a bile salt, have been used to reduce unwanted accumulations of fat. Recent in vitro and ex vivo investigations indicate that deoxycholate alone causes adipocyte lysis. OBJECTIVE: We sought to report our experience treating lipomas using subcutaneous deoxycholate injections. METHODS: A total of 6 patients presenting with 12 lipomas were treated with intralesional injections of sodium deoxycholate (1.0%, 2.5%, and 5.0%) at intervals of 2 to 20 weeks. Tumor size, cutaneous reactions, and patients' subjective responses were recorded before and after treatment. RESULTS: All lipomas decreased in size (mean area reduction, 75%; range, 37%-100%) as determined by clinical measurement (with ultrasound confirmation in one lipoma) after an average of 2.2 treatments. Several lipomas fragmented or became softer in addition to decreasing in volume. Adverse effects, including transient burning, erythema, and local swelling, were associated with higher deoxycholate concentrations but resolved without intervention. There was no clear association between deoxycholate concentration and efficacy. CONCLUSIONS: Our clinical experience supports our laboratory investigations demonstrating that deoxycholate, rather than phosphatidylcholine, is the active ingredient in subcutaneously injected formulas used to treat adipose tissue. This small series suggests that low concentration deoxycholate may be a relatively safe and effective treatment for small collections of fat. However, controlled clinical trials will be necessary to substantiate these observations.

Adult↗

PubMed2005

Wild-type blocking polymerase chain reaction for detection of single nucleotide minority mutations from clinical specimens.

Detection and sequencing of mutations from clinical specimens is often complicated by the presence of an excess of nonmutated cells. To facilitate the detection and sequencing of minority mutations from clinical specimens, we developed wild-type blocking polymerase chain reaction (WTB-PCR). This technique allows sensitive detection of minority mutations in a tissue sample containing excess wild-type DNA. In WTB-PCR, a nonextendable locked nucleic acid (LNA) oligonucleotide binds tightly to a region of wild-type DNA known to develop point mutations. This LNA sequence blocks amplification of wild-type DNA during PCR while permitting amplification of mutant exon 15. Our results show that the LNA blocking oligonucleotide inhibits amplification of wild-type DNA in a dose-dependent manner. WTB-PCR was able to detect mutant DNA in clinical samples of melanoma tissue containing an excess of nonmelanoma cells. This method was also able to detect small amounts of point mutated or tandem mutated DNA diluted with a much larger concentration of wild-type DNA. This rapid and simple assay overcomes the limitations of current methods to detect minority mutations. The potential applications of WTB-PCR include early diagnosis and prognosis of various cancers.

Base Sequence↗

PubMed2005

Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab.

Acne fulminans is a syndrome of sudden onset hemorrhagic and ulcerative acne involving the back, chest, and face combined with systemic symptoms. It can be the dermatologic manifestation of the synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome. Current therapy for acne fulminans consists of wound care, topical and systemic corticosteroids, isotretinoin, and nonsteroidal anti-inflammatory drugs (NSAIDs). Infliximab, a recently developed monoclonal antibody against tumor necrosis factor-alfa, has shown efficacy in the treatment of psoriatic arthritis and ankylosing spondylitis both of which share clinical similarities to the SAPHO syndrome. We report the case of a patient with the SAPHO syndrome and acne fulminans who was treated with infliximab. Ten months after initiating therapy with infliximab, the area of the patient's ulcerative lesions was reduced by 70%. Infliximab might be considered as a treatment option for patients with acne fulminans unresponsive to conventional therapies.

Acne Vulgaris↗

PubMed2005

Bioluminescent imaging of melanoma in live mice.

Melanoma is highly resistant to conventional chemotherapeutic agents and novel therapeutic approaches are needed. Current animal models of melanoma in animals are sub-optimal. The most commonly used homograft model is the B16 mouse melanoma. Evaluation of potential melanoma therapies with this model is limited by the inaccuracy of caliper measurement of subcutaneous tumors, of counting lung nodules in metastasis models, and the indirect nature of "survival" curves when studying brain metastases. We have developed and characterized an accurate, sensitive, and reproducible bioluminescent B16 melanoma model that allows for serial, real-time analyses of tumor burden in live mice. We demonstrate that this model is applicable to subcutaneous tumors, lung metastases, and intracranial tumors and offers a solution to many of the limitations of previous models. As proof of principle, we use this model to show the efficacy of a live, Listeria monocytogenes vaccine expressing the melanoma antigen tyrosinase-related protein-2 to protect mice against intravenous B16 melanoma challenge. Additionally, we extend our approach to include the human A375 melanoma model and are able to show in vivo differences between sub-lines with varying metastatic potential. These models represent an accurate and reproducible means for in vivo melanoma monitoring in preclinical studies.

Animals↗

PubMed2004

Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution.

BACKGROUND: Phosphatidylcholine injections are becoming an increasingly popular technique to treat localized fat accumulation. This formula is composed primarily of phosphatidylcholine and sodium deoxycholate, a bile salt used to solubilize the natural phospholipid in water. The mechanism through which this injectable phosphatidylcholine formulation causes localized fat reduction is unknown. OBJECTIVE: To investigate the active component and mechanism of action of an injectable phosphatidylcholine formulation in clinical use. METHODS: Cell viability and cell membrane lysis assays were performed on cell cultures and porcine skin after treatment with the phosphatidylcholine formula, isolated sodium deoxycholate, or common laboratory detergents Triton-X 100 and Empigen BB. In addition, we described the histologic changes after injection of these substances into porcine tissue. RESULTS: A significant and comparable loss of cell viability, cell membrane lysis, and disruption of fat and muscle architecture was seen in cell cultures and tissue specimens treated with the phosphatidylcholine formula and isolated sodium deoxycholate. These findings were similar to the effects produced after treatment with laboratory detergents. CONCLUSIONS: The phosphatidylcholine formula popularly used in subcutaneous injections for fat dissolution works primarily as a detergent causing nonspecific lysis of cell membranes. Our findings suggest that sodium deoxycholate is the major active component responsible for cell lysis. Detergent substances may have a role in eliminating unwanted adipose tissue. It is advised that physicians use caution until adequate safety data are available.

Adipose Tissue↗

PubMed2003

Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade.

The Ras-Raf-MAPK pathway is constitutively activated in the majority of melanomas because of a mutation in the BRAF gene. It has been hypothesized that activation of this pathway is crucial for the genesis and maintenance of melanoma and therefore represents an attractive clinical target for metastatic disease. We synthesized a previously characterized MAP kinase kinase inhibitor to test the effect that blocking the Ras-Raf-MAPK pathway would have on the establishment and maintenance of melanoma metastases. Oral administration of CI 1040 inhibited formation of pulmonary metastases and caused rapid regression of established pulmonary metastases in the mouse. Our findings indicate that Ras-Raf-MAPK activation provides crucial signals for the survival of melanoma cells at ectopic sites and that the pharmacological inhibition of this pathway is a promising target for melanoma therapy.

Animals↗

PubMed2003

Atorvastatin prevents RhoC isoprenylation, invasion, and metastasis in human melanoma cells.

Melanoma is a deadly cancer due to its propensity to metastasize. Pharmacological inhibition of cell motility may benefit patients with cutaneous melanoma by preventing metastasis to internal organs. The Rho GTPases are signaling molecules that drive metastasis by controlling cell motility. We found RhoC to be expressed in clinical melanoma specimens and hypothesized that inhibiting its activation might prevent metastasis. Some Rho proteins, such as RhoC, depend on posttranslational geranylgeranylation for biological activity. We investigated the effect that Atorvastatin, a 3-hydroxy 3-methylglutaryl CoA (HMG-CoA) reductase inhibitor that prevents Rho geranylgeranylation, had on subcellular localization and activity of Rho proteins as well as the metastatic ability of melanoma cells. Atorvastatin inhibited Rho activation and reverted the metastatic phenotype of human melanoma cells in vitro. Moreover, Atorvastatin, at plasma levels comparable to those used to treat of hypercholesterolemia, inhibited in vivo metastasis of melanoma cells overexpressing RhoC. These results support further examination of statins for primary prophylaxis of melanoma metastasis.

Animals↗

PubMed2002

Isoprenylation is necessary for the full invasive potential of RhoA overexpression in human melanoma cells.

Rho GTPases are signaling molecules known to control cell motility. Several recent studies have suggested a role for Rho proteins in mediating tumor metastasis independent of their affects on cell proliferation. As Rho proteins require post-translational modification with a geranlygeranyl moiety for full activity, we tested the affect of blocking geranylation on localization, downstream signaling, and stimulation of invasion. Expression of a constitutively active Rho construct in A375 melanoma cells dramatically stimulated invasion through Matrigel membranes; however, a constitutively active RhoA mutated so that it cannot be geranylated, failed to stimulate invasion. Moreover, expression of epitope or GFP tagged modifications of this nongeranylatable constitutively active Rho demonstrated that geranylation is necessary for correct cellular localization of Rho. Geranylation was also found to be necessary for full downstream activation of serum response factor mediated transcription. Pharmacologic inhibition of Rho geranylation produced similar inhibition of Rho localization, signaling, and invasion. Our results suggest that inhibition of Rho geranylation may be an attractive pharmacologic target for inhibiting melanoma metastasis.

Animals↗