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Blood. 2003 Mar 1;101(5):1962-9. Epub 2002 Oct 24.
CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes.

Granziero L, Circosta P, Scielzo C, Frisaldi E, Stella S, Geuna M, Giordano S, Ghia P, Caligaris-Cappio F.

Department of Oncological Sciences, University of Torino, Institute for Cancer Research and Treatment (IRCC), Candiolo (TO) and Division of Clinical Immunology and Hematology, Ospedale Mauriziano Umberto I, Torino, Italy.

Growth and survival of chronic B-cell tumors are favored by the malignant cell's capacity to respond to selected microenvironmental stimuli provided by nontumoral bystander cells. To investigate which mechanisms operate in these crosstalks and whether they are malignancy-related or reproduce the mechanisms used by normal B cells we have studied the expression and functional role of semaphorin CD100 (now called Sema4D) in chronic lymphocytic leukemia (CLL) cells and normal CD5+ B cells. We demonstrate here that (1) leukemic and normal CD5+ B lymphocytes uniformly express CD100; (2) the CD100 high-affinity receptor Plexin-B1 is expressed by bone marrow stromal cells, follicular dendritic cells, and activated T lymphocytes, and is thus available to CD100+ lymphocytes in different specific microenvironments; and (3) upon interaction between CD100 and Plexin-B1 both CLL and normal CD5+ B cells increase their proliferative activity and extend their life span. These findings establish that Plexin-B1 is an easily accessible receptor for CD100 within the immune system. The encounter of CD100+ leukemic cells with Plexin-B1 may promote the proliferation and survival of malignant cells. The crosstalk operated by the CD100/Plexin-B1 interaction is not malignancy related but reproduces a mechanism used by normal CD5+ B cells.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12406905&dopt=Abstract



Int Immunol. 2002 Nov;14(11):1247-53.
Macrophages as main inducers of IFN-gamma in T cells following administration of human and mouse heat shock protein 60.

Breloer M, More SH, Osterloh A, Stelter F, Jack RS, Bonin Av A.

Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht Strasse 74, 20359 Hamburg, Germany.

Human Hsp60 (hHsp60) elicits a potent pro-inflammatory response in cells of the innate immune system. Here we compared the capacity of peritoneal exudate cells (PEC) and bone marrow-derived dendritic cells (DC) to stimulate murine T cells in the presence of Hsp60. Hsp60 induced a specific secretion of high amounts of IFN-gamma in T cells with PEC as antigen-presenting cells (APC). Although DC are highly efficient APC, they were much less potent as inducers of IFN-gamma in the presence of Hsp60. The IFN-gamma-inducing effect of Hsp60 is dependent on co-stimulatory signals provided by B7-CD28 interactions. In addition to hHsp60, we used syngenic murine recombinant Hsp60 (mHsp60) and show that mHsp60 also induces IFN-gamma in TCR transgenic T cells. These results demonstrate that mHsp60 as an endogenous 'self' molecule can induce an inflammatory response. Interestingly, mHsp60, although sharing >98% protein sequence identity with the hHsp60 homologue, does not bind to human CD14 molecules. Taken together, our results indicate a finely tuned activation of cells from the innate and adaptive immune system by 'self' Hsp60 that depends strongly on the type of APC.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12407015&dopt=Abstract



Dig Liver Dis. 2002 Sep;34 Suppl 2:S12-8.
Variation in human intestinal microbiota with age.

Hopkins MJ, Sharp R, Macfarlane GT.

MRC Microbiology and Gut Biology Group, University of Dundee Medical School, Dundee, UK. m.j.hopkinundee.ac.uk

The large intestinal microbiota plays an important role in normal bowel function and the maintenance of host health, through the formation of short chain fatty acids, modulation of immune system reactivity and development of colonisation resistance. However, the effects of ageing on bacterial community structure in the colon are not well documented. Aim of this study is to assess bacterial species diversity in the human faecal microbiota with respect to age and Clostridium difficile infection. Bacterial populations were quantified from stool samples obtained from children (16 months to seven years), young adults (21-34 years), healthy elderly people (67-88 years) and patients diagnosed with Clostridium difficile-associated diarrhoea (68-73 years). Microbial diversity was assessed to species level for samples from the latter three subject groups. Marked interindividual variations occurred in microbial composition at genus and species levels. The faecal microbiota of children was found to be bacteriologically less complex whilst advancing age was associated with decreased bifidobacteria and increased bacteroides species diversity. Changes in microbial composition with age or disease will alter the metabolic capacity of the gut microbiota and has important implications for therapies aimed at modulating the large intestinal microbiota.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12408433&dopt=Abstract



Mar Environ Res. 2002 Sep-Dec;54(3-5):559-63.
Impact of polychlorinated biphenyls (PCBs) on the immune function of fish: age as a variable in determining adverse outcome.

Duffy JE, Carlson E, Li Y, Prophete C, Zelikoff JT.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo 10987, USA.

Polychlorinated biphenyls (PCBs) are a major contaminant of global extent in water resources and aquatic biota. Due to its high lipid solubility, PCBs fail to be degraded and, therefore, continue to bioaccumulate throughout the environment and food chain. To determine the impact of PCBs on the immune system of aged and juvenile Japanese medaka (Oryzias latipes), fish were injected with the coplanar PCB congener 126 and examined after 3 and 14 days. PCB 126 produced oxidative stress in both age groups of fish 14 days post-injection; however, juvenile medaka appeared more susceptible than aged fish. Humoral immunity, as determined by antibody forming cell (AFC) numbers, was significantly depressed for up to 14 days post-injection in both age groups. These results demonstrate the sensitivity of the fish immune response for predicting PCB-induced immunotoxicity and identify age as a variable in determining adverse outcome.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12408617&dopt=Abstract



Methods Cell Sci. 2001;23(4):175-84.
Comparing qualitative and quantitative spectroscopic techniques for the detection of the effect of direct iron loading of mammalian cell cultures.

Traore HN, Meyer D.

Biochemistry Division, Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland-Park, 2006 Johannesburg, South Africa.

Iron overload augments diseases of the liver and microorganism infection as well as deregulates the immune system. In vitro analysis of the effects of iron loading and its chelation involves determining the amount of iron constituting overload, which metal sources and cell lines to use and reliable assay methods. The uptake of 500 microM FeSO4 or FeEDTA by CEMss, U937 or leukocytes was confirmed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Excess iron increased CEMss viability (assessed by MTT, XTT, Trypan- and Alamar Blue) by an average of 18% (P = 0.034). Flow cytometry indicated dye-viable cells to be undergoing apotosis/necrosis while still confirming an increase (9%, P < 0.001) in excess iron-induced viability. The iron chelator desferioxamine (DFO) when added in addition to Fe, reversed the effects of excess iron (and vice versa) and had detrimental effects when used on its own (33% inhibition of viability as measured by dyes and 10.85%; P = 0.0427 assessed by flow cytometry). The 4 dyes demonstrated different levels of sensitivity in detecting the influence of iron or DFO but gave a related, qualitative picture while flow cytometry and ICP-AES data was more quantitative.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12486327&dopt=Abstract








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