Extralymphatic Filariasis.

Filariasis caused by nematodes affects the structure and function of lymphatic vessels. Lymphedema due to lymphatic blockage and lymphadenitis is the usual mode of presentation of filariasis. However, rarely extralymphatic filariasis has been reported in uncommon sites, including skin and soft tissue.

Comparison of 5% minoxidil lotion monotherapy versus its combination with autologous platelet rich plasma in androgenetic alopecia in hundred males.

Background: Androgenetic alopecia (AGA) is the most common form of alopecia in men, affecting 70% by the age of 20 years. The present study was conducted with the objective of comparing the efficacy of monotherapy with topical 5% minoxidil and its combination with intradermal platelet rich plasma (PRP), in male AGA.

Methods: This observational study was conducted at the dermatology department of a tertiary care hospital over a duration of 2 years.

Adenosine deaminase modulates metabolic remodeling and orchestrates joint destruction in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models.

Power Law Based "Out of Body" Tactile Funneling for Mobile Haptics.

''Out of body" tactile illusions can serve as a tool to exploit the limitations of human perception to augment the information displayed in the mobile haptic devices. The objective of this study was to establish a psychophysics based mathematical relationship between the intensity of physical and phantom stimulus rendered "out of the body." In order to achieve this objective, three experiments were conducted, the first experiment was to compare three existing algorithms (linear, logarithmic, and square) defined for "on the body" when extended to "out of the body," the second experiment was to test the pertinence of the best performing algorithm from first experiment, and the third experiment was designed to identify an ideal mathematical relation using psychophysical studies.

Perianal Block: Is It as Good as Spinal Anesthesia for Closed Hemorrhoidectomies?

Background And Aims: This study compared if perianal block using ropivacaine and dexmedetomidine was as good as spinal anesthesia (SA) using bupivacaine (heavy) for closed hemorrhoidectomies.

Methods: A prospective randomized study was conducted in sixty patients who underwent closed hemorrhoidectomy. Thirty patients of Group A received SA.

A rare case of unilateral eosinophilic fasciitis associated with ipsilateral extragenital lichen sclerosus.

Eosinophilic fasciitis, also known as Shulman's syndrome, is a fibrosing scleroderma-like syndrome, which is a distinct entity. A 55-year-old man, presented with progressive skin darkening, thickening, and tightening over the left lower limb since 6 months. Dermatological examination revealed a hyperpigmented indurated area on the left thigh, extending to the anterior aspect of the left leg.

PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion.

Genome-wide functional genetic screen with the anticancer agent AMPI-109 identifies PRL-3 as an oncogenic driver in triple-negative breast cancers.

Triple-negative breast cancers (TNBC) are among the most aggressive and heterogeneous cancers with a high propensity to invade, metastasize and relapse. Here, we demonstrate that the anticancer compound, AMPI-109, is selectively efficacious in inhibiting proliferation and inducing apoptosis of multiple TNBC subtype cell lines as assessed by activation of pro-apoptotic caspases-3 and 7, PARP cleavage and nucleosomal DNA fragmentation. AMPI-109 had little to no effect on growth in the majority of non-TNBC cell lines examined.

Livedoid Vasculopathy with Hyperhomocysteinemia Responding to Hyperbaric Oxygen Therapy.

A 30-year-old male presented to the dermatology department with complaints of multiple ulcers over both legs of 6 years duration. The ulcers had a waxing and waning course with present exacerbation of lesions since 1 month. Dermatological examination revealed multiple ulcers distributed in a reticular pattern over medial and lateral aspects of both lower legs, extensor aspect of both ankles and dorsum of both feet.

A Rare Case of Plantar Epithelioma Cuniculatum Arising from a Wart.

A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul smelling cheesy material.

1,25-Dihydroxyvitamin D3-3-bromoacetate, a novel vitamin D analog induces immunosuppression through PI3K/Akt/mTOR signaling cascade.

Purpose: The molecular mechanism responsible for the immunomodulatory effect of 1,25-dihydroxyvitamin D3 (Vit-D) is still not well elucidated. Unavoidable systemic toxicity of Vit-D has encouraged to develop more potent and less toxic Vit-D analogs, such as 1,25-dihydroxyvitamin D3-3-bromoacetate (BE). Our aim was to explore the immunosuppressive effect of BE and its molecular mechanism in autoimmune diseases.

1α,25-Dihydroxyvitamin-D3-3-bromoacetate regulates AKT/mTOR signaling cascades: a therapeutic agent for psoriasis.

The efficacy of 1α,25-dihydroxyvitamin D3 (Vit-D) limits its topical use despite its profound effects on cellular differentiation, proliferation, and immunomodulation. Therefore, in search for a more effective analog of Vit-D, in this study we have evaluated the antiproliferative and proapoptotic effects of 1α,25-dihydroxyvitamin D3-3-bromoacetate (BE). Proliferation and apoptosis studies in normal human epidermal keratinocytes (NHEKs) were conducted by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), CFSE (carboxy fluorescein succinimidyl ester) dilution, and Annexin V assays.

Effect of dietary vitamin D and calcium on the growth of androgen-insensitive human prostate tumor in a murine model.

Vitamin D deficiency has been associated with increased risk of prostate cancer (PC) in epidemiologic and prospective studies. An association has also been made between high dietary calcium and increased PC risk. In this study, we evaluated the effect of dietary vitamin D and calcium on the growth of human androgen-insensitive prostate tumor in an athymic mouse model.

Internalization of a C17α-alkynylestradiol-porphyrin conjugate into estrogen receptor positive MCF-7 breast cancer cells.

We hypothesized that expression of nuclear estrogen receptor (ER) in hormone-sensitive breast cancer cells could be harnessed synergistically with the tumor-accumulating effect of porphyrins to selectively deliver estrogen-porphyrin conjugates into breast tumor cells, and preferentially kill tumor cells upon exposure to visible light. In this study we synthesized a conjugate of C(17α)-alkynylestradiol and pyropheophorbide and demonstrated that this conjugate is internalized by ER-positive MCF-7 cells while pyropheophorbide did not, suggesting an ER-mediated uptake and internalization of the conjugate by incipient nuclear ER in MCF-7 cells. This study is a direct demonstration of our hypothesis about ER-mediated internalization of estrogen-porphyrin conjugates.

1α,25-Dihydroxyvitamin D3-3β-bromoacetate, a potential cancer therapeutic agent: synthesis and molecular mechanism of action.

Synthesis of 1α,25-dihydroxyvitamin D(3)-3β-bromoacetate (1,25(OH)(2)D(3)-3-BE), a potential anti-cancer agent is presented. We also report that mechanism of action of 1,25(OH)(2)D(3)-3-BE may involve reduction of its catabolism, as evidenced by the reduced and delayed expression of 1α,25-dihydroxyvitamin D(3)-24-hydroxylase (CYP24) gene in cellular assays.

A vitamin D receptor-alkylating derivative of 1α,25-dihydroxyvitamin D3 inhibits growth of human kidney cancer cells and suppresses tumor growth.

1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃] has shown strong promise as an antiproliferative agent in several malignancies, yet its therapeutic use has been limited by its toxicity leading to search for analogues with antitumor property and low toxicity. In this study, we evaluated the in vitro and in vivo properties of 1,25-dihydroxyvitamin D₃-3-bromoacetate [1,25(OH)₂D₃-3-BE], an alkylating derivative of 1,25(OH)₂D₃, as a potential therapeutic agent for renal cancer. Dose response of 1,25(OH)₂D₃-3-BE in 2 kidney cancer cell lines was evaluated for its antiproliferative and apoptotic properties, and mechanisms were evaluated by Western blot and FACS analyses.

Anti-growth effect of 1,25-dihydroxyvitamin D3-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside in pancreatic cancer cells.

1,25-Dihydroxyvitamin D(3)-3-bromoacetate (1,25(OH)(2)D(3)-3-BE) is a vitamin D receptor-alkylating derivative of 1,25(OH)(2)D(3). The strong dose-dependent antiproliferative and apoptotic effects of this compound in androgen-sensitive and androgen-insensitive prostate cancer cells have been reported. In this communication, it is reported that 1,25(OH)(2)D(3)-3-BE strongly inhibits the growth of several pancreatic cancer cell lines.

Covalent labeling of nuclear vitamin D receptor with affinity labeling reagents containing a cross-linking probe at three different positions of the parent ligand: structural and biochemical implications.

Structure-functional characterization of vitamin D receptor (VDR) requires identification of structurally distinct areas of VDR-ligand-binding domain (VDR-LBD) important for biological properties of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). We hypothesized that covalent attachment of the ligand into VDR-LBD might alter 'surface structure' of that area influencing biological activity of the ligand. We compared anti-proliferative activity of three affinity alkylating derivatives of 1,25(OH)(2)D(3) containing an alkylating probe at 1,3 and 11 positions.

Fatty acid-binding site environments of serum vitamin D-binding protein and albumin are different.

Vitamin D-binding protein (DBP) and albumin (ALB) are abundant serum proteins and both possess high-affinity binding for saturated and unsaturated fatty acids. However, certain differences exist. We surmised that in cases where serum albumin level is low, DBP presumably can act as a transporter of fatty acids.

Cross-talk among structural domains of human DBP upon binding 25-hydroxyvitamin D.

Serum vitamin D-binding protein (DBP) is structurally very similar to serum albumin (ALB); both have three distinct structural domains and high cysteine-content. Yet, functionally they are very different. DBP possesses high affinity for vitamin D metabolites and G-actin, but ALB does not.

Mechanistic and pharmacodynamic studies of a 25-hydroxyvitamin D3 derivative in prostate cancer cells.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active form of vitamin D has strong antiproliferative effects in cancer cells. But it is highly toxic at therapeutic doses. We have observed that 25-hydroxyvitamin D(3)-3-bromoacetate (25-OH-D(3)-3-BE), a derivative of 25-hydroxyvitamin D(3), the pro-hormonal form of 1,25(OH)(2)D(3) has strong growth-inhibitory and proapoptotic properties in hormone-sensitive and hormone-refractory prostate cancer cells.

Photodynamic cell-kill analysis of breast tumor cells with a tamoxifen-pyropheophorbide conjugate.

We hypothesized that estrogen receptor (ER) in hormone-sensitive breast cancer cells could be targeted for selective photodynamic killing of tumor cell with antiestrogen-porphyrin conjugates by combining the over-expression of ER in hormone-sensitive breast cancer cells and tumor-retention property of porphyrin photosensitizers. In this study we describe that a tamoxifen (TAM)-pyropheophorbide conjugate that specifically binds to ER alpha, caused selective cell-kill in MCF-7 breast cancer cells upon light exposure. Therefore, it is a potential candidate for ER-targeted photodynamic therapy of cancers (PDT) of tissues and organs that respond to estrogens/antiestrogens.

Nuclear estrogen receptor targeted photodynamic therapy: selective uptake and killing of MCF-7 breast cancer cells by a C17alpha-alkynylestradiol-porphyrin conjugate.

We hypothesized that over-expression of estrogen receptor (ER) in hormone-sensitive breast cancer could be harnessed synergistically with the tumor-migrating effect of porphyrins to selectively deliver estrogen-porphyrin conjugates into breast tumor cells, and preferentially kill the tumor cells upon exposure to red light. In the present work we synthesized four (4) conjugates of C17-alpha-alkynylestradiol and chlorin e6-dimethyl ester with varying tether lengths, and showed that all these conjugates specifically bound to recombinant ER alpha. In a cellular uptake assay with ER-positive MCF-7 and ER-negative MDA-MB 231 human breast cancer cell-lines, we observed that one such conjugate (E17-POR, XIV) was selectively taken up in a dose-dependent and saturable manner by MCF-7 cells, but not by MDA-MB 231 cells.