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Saeed R Khan

Publications and source records attributed to Saeed R Khan.

At least 37 records · Page 2Linked to original sources
PubMed2005

Sesquiterpenes: natural products that decrease cancer growth.

Despite recent advances in our understanding of the biological processes leading to the development of cancer, there is still a need for new and effective agents to help bring this disease under control. One of the oldest and most effective strategies for developing new chemotherapeutics is the isolation and evaluation of chemicals of natural origin. The importance of natural products for drug discovery has been impressive: One has to only look at the number of clinically active drugs that are used in cancer therapy to see how many are either natural products or are based on natural products. It is also apparent that materials from natural sources are excellent probes (indicators) for cellular targets that, when modulated, may have a deleterious effect upon the survival or proliferation of tumor cells. And the search goes on. Sesquiterpenes are a class of naturally occurring molecules that have demonstrated therapeutic potential in decreasing the progression of cancer. These molecules are 15-carbon isoprenoid compounds that are typically found in plants and marine life. Although this class of compounds has frequently provided encouraging leads for chemotherapeutics, they have not been evaluated as potential anticancer agents. In this review, we provide a current overview of sesquiterpenoids that have potential as anticancer agents.

Animals↗
PubMed2004

Synthesis and evaluation of aminophosphinic acid derivatives as inhibitors of renal dipeptidase.

Renal dipeptidase (RDP) is an enzyme overexpressed in benign and malignant colorectal tumors. In an effort to identify potent inhibitors of this enzyme, a series of aminophosphinic acid derivatives were synthesized. Compounds 3a and 3c in which the phenyl ring was para substituted with F and Br and olefin with Z geometry, showed better inhibitory activity against RDP enzyme (IC50 = 5-6 nM).

Alkenes↗
PubMed2004

Synthesis and antitumor evaluation of benzoylphenylurea analogs.

Novel series of benzoylphenylurea analogs 7-10 were prepared and evaluated for in vitro cytotoxic activity against a panel of eight different human cancer cell lines. A very interesting inhibition profile against BxPC3, Mia-Paca, and Hep2 cells with compound 10 has been observed. Compounds 8 and 9 showed the significant cytotoxicity in Hep2 cells. All cell lines were resistant to compound 7.

Antineoplastic Agents↗
PubMed2004

Modulators of urinary stone formation.

Urine contains compounds that modulate the nucleation, growth and aggregation of crystals as well as their attachment to renal epithelial cells. These compounds may function to protect the kidneys against: 1, the possibility of crystallization in tubular fluid and urine, which are generally metastable with respect to calcium salts, 2, crystal retention within the kidneys thereby preventing stone formation and 3, possibly against plaque formation at the nephron basement membrane. Since oxalate is the most common stone type, the effect of various modulators on calcium oxalate (CaOx) crystallization has been examined in greater details. Most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans while nucleation promotion activity is most likely sustained by membrane lipids. Nephrocalcin, Tamm-Horsfall protein, osteopontin, urinary prothrombin fragment 1, and bikunin are the most studied inhibitory proteins while chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) are the best studied glycosaminoglycans. Crystallization modulating macromolecules discussed here are also prominent in cell injury, inflammation and recovery. Renal epithelial cells on exposure to oxalate and CaOx crystals produce some of the inflammatory molecules such as monocyte chemoattractant protein-1 (MCP-1) with no apparent role in crystal formation. In addition, macrophages surround the CaOx crystals present in the renal interstitium. These observations indicate a close relationship between inflammation and nephrolithiasis.

Calcium Oxalate↗
PubMed2004

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies.

Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin-angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor kappabeta. Urate crystals also stimulate the macrophages to produce MMPs.

Animals↗
PubMed2004

Effect of angiotensin II receptor blockage on osteopontin expression and calcium oxalate crystal deposition in rat kidneys.

Hyperoxaluria leads to calcium oxalate (CaOx) crystallization and development of tubulointerstitial lesions in the kidneys. Treatment of hyperoxaluric rats with angiotensin II (Ang II) type I receptor blocker (ARB) reduces lesion formation. Because Ang II mediates osteopontin (OPN) synthesis, which is involved in both macrophage recruitment and CaOx crystallization, it was hypothesized that ARB acts via OPN. Hyperoxaluria was induced in 10-wk-old male Sprague-Dawley rats, and they were treated with ARB candesartan. At the end of 4 wk, kidneys were examined for crystal deposits, ED-1-positive cells, and expression of OPN mRNA. PCR was used to quantify OPN, renin, and angiotensin-converting enzyme (ACE) mRNA in kidneys. RIA was used to determine renal, plasma, and urinary OPN; plasma renin; Ang II and ACE; and renal Ang II. For evaluating oxidative stress, malondialdehyde was measured. Urinary calcium, oxalate, creatinine, and albumin were also determined. Despite similar urinary calcium and oxalate levels, kidneys of hyperoxaluric rats on candesartan had fewer CaOx crystals, fewer ED-1-positive cells, reduced OPN expression, and reduced malondialdehyde than hyperoxaluric rats. Urinary albumin excretion and serum creatinine levels improved significantly on candesartan treatment. mRNA for OPN, renin, and ACE were significantly elevated in hyperoxaluric rats. OPN synthesis and production increased with hyperoxaluria but to a lesser extent in candesartan-treated hyperoxaluric rats. These results show for the first time that oxalate can activate the renal renin-angiotensin system and that oxalate-induced upregulation of OPN is in part mediated via renal renin-angiotensin system.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Role of renal epithelial cells in the initiation of calcium oxalate stones.

Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E(2), which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.

Animals↗
PubMed2003

Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer.

BACKGROUND: Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells. METHODS: We coupled a chemically modified form of thapsigargin, L12ADT, to a peptide carrier that is a substrate for the prostate-specific antigen (PSA) protease to produce a soluble, cell-impermeant latent prodrug that is specifically activated extracellularly within metastatic prostate cancer sites by PSA. We analyzed the kinetics of PSA hydrolysis of the prodrug, the in vitro cytotoxicity of the prodrug against PSA-producing LNCaP human prostate cancer and PSA non-producing HCT-116 human colon cancer cells, and the in vivo pharmacokinetics of the prodrug in mice. We also analyzed antitumor efficacy of the prodrug in nude mice xenograft models of prostate cancer (using LNCaP cells) and renal carcinoma (using human SN12C cells). RESULTS: The L12ADT peptide prodrug was hydrolyzed efficiently by PSA, was selectively toxic to PSA-producing prostate cancer cells in vitro, and was stable in human plasma. A single dose of 7 mg/kg resulted in a peak serum prodrug concentration of 15.4 +/- 1.1 microM and a half-life of approximately 2.8 hours. Over 24 hours, less than 0.5% of free L12ADT was observed in plasma. Levels of prodrug and liberated L12ADT in prostate cancer xenograft tumors were approximately eightfold and sixfold, respectively, higher than the in vitro LD50s. Prostate cancer xenograft tumors in mice treated with prodrug by intravenous administration were growth-inhibited without substantial host toxicity. Continuous subcutaneous prodrug administration in mice produced complete growth inhibition of established PSA-producing prostate cancer xenograft tumors but had no effect on PSA non-producing renal carcinoma xenograft tumors. CONCLUSION: Further development of PSA-activated thapsigargin prodrugs as therapy for metastatic prostate cancer is warranted.

Animals↗
PubMed2003

Protective role of heparin/heparan sulfate on oxalate-induced changes in cell morphology and intracellular Ca2+.

Alterations in intracellular Ca2+ ([Ca2+]i) are generally associated with cellular distress. Oxalate-induced cell injury of the renal epithelium plays an important role in promoting CaOx nephrolithiasis. However, the degree of change in intracellular free calcium ions in renal epithelial cells during oxalate exposure remains unclear. The aim of this study is to determine whether acute short-term exposure to oxalate produces morphological changes in the cells, induces a change in cytosolic Ca2+ levels in renal tubular epithelial cells and whether the application of extracellular glycosaminoglycans (GAGs) prevents these changes. Cultured Mardin-Darby canine kidney cells were exposed to oxalate, and changes in cytosolic Ca2+ were determined under various conditions. The effect of heparin and heparan sulfate (HS) during oxalate exposure was examined. The change in the GAG contents of the culture medium was also determined. Transmission electron microscopy (TEM) was performed for morphological analysis. The degree of change in cytosolic Ca2+ strongly correlated with oxalate concentration. Cytosolic Ca2+ levels decreased in parallel with an increase in the concentration of oxalate. However, this decrease was strongly inhibited by pretreatment with heparin or HS. TEM revealed cytoplasmic vacuolization, the appearance of flocculent material and mitochondrial damage after oxalate exposure. On the other hand, pretreatment with heparin or HS completely blocked these morphological changes. The present data suggest that acute exposure to a high concentration of oxalate challenges the renal cells, diminishes their viability and induces changes in cytosolic Ca2+ levels. Heparin and HS, which are known as potent inhibitors of CaOx crystallization, may also prevent oxalate-induced cell changes by stabilizing the cytosolic Ca2+ level.

Animals↗
PubMed2003

Calcium phosphate-induced renal epithelial injury and stone formation: involvement of reactive oxygen species.

BACKGROUND: Crystal formation and retention are critical events for the formation of kidney stones. Oxalate and calcium oxalate (CaOx) crystals are injurious to renal epithelium, and membranes of injured cells promote crystal adherence and retention. Calcium phosphate (CaP) is the most common crystal in both urine and stones, most likely to form in the early segments of the nephron and can nucleate CaOx in a metastable solution. We hypothesized that CaP can also injure the renal epithelial cells. METHODS: We exposed proximal tubular origin line derived from pig proximal tubules (LLC-PK1), and collecting duct origin Madin-Darby canine kidney (MDCK) cell lines to various concentrations of Brushite (Br) crystals and investigated staining with Trypan Blue and the release of lactate dehydrogenase (LDH) into the medium as an indicator of injury. In order to determine the involvement of reactive oxygen species, we also measured LDH release in the presence of superoxide dismutase (SOD) and production of hydrogen peroxide (H2O2) and 8-isoprostane (8-IP) in the presence of the catalase. RESULTS: Exposure to Br crystals was associated with LDH release by both cell types, induced the production of H2O2 and 8-IP. Presence of SOD and catalase reduced LDH release as well as staining with trypan blue. Catalase was also associated with reduced production of H2O2 and 8-IP. CONCLUSION: Brushite crystals are injurious to cells of both the proximal tubules as well as collecting ducts. Injury is mediated by reactive oxygen species. We propose that CaP crystals can independently interact with renal epithelium, promote sites for crystal attachment, and then either grow into mature CaP stones or create sites for CaOx crystal nucleation, retention, and stone development.

Animals↗
PubMed2003

Increased expression of monocyte chemoattractant protein-1 (MCP-1) by renal epithelial cells in culture on exposure to calcium oxalate, phosphate and uric acid crystals.

BACKGROUND: During the development of non-infectious kidney stones, crystals form and deposit in the kidneys and become surrounded by monocytes/macrophages (M/M). We have proposed that in response to crystal exposure renal epithelial cells produce chemokines, which attract the M/M to the sites of crystal deposition. We investigated the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein by NRK52E rat renal tubular epithelial cells exposed to calcium oxalate (CaOx), brushite (Br, a calcium phosphate) and uric acid (UA) crystals. METHODS: Confluent cultures of NRK52E cells were exposed to CaOx, Br or UA at a concentration of 250 micro g/ml (66.7 micro g/cm(2)). They were exposed for 1, 3, 6, 12, 24 and 48 h for isolation of mRNA and 24 h for ELISA to determine the secretion of protein into the culture medium. Since cells are known to produce free radicals on exposure to CaOx crystals we also investigated the effect of free radical scavenger catalase on the crystal induced expression of MCP-1 mRNA and protein. RESULTS: Exposure of NRK52E cells to the crystals resulted in increased expression of MCP-1 mRNA and production of the chemoattractant. CaOx crystals were most provocative while UA the least. Treatment with catalase had a negative effect on the increased expression of both MCP-1 mRNA and protein, which indicates the involvement of free radicals in up-regulation of MCP-1 production. CONCLUSION: Exposure to both CaOx and calcium phosphate crystals stimulates increased production of MCP-1. Free radicals appear to be involved in this up-regulation. Results indicate that MCP-1, which is often associated with localized inflammation, may be one of the chemokine mediators associated with the deposition of various urinary crystals in the kidneys during kidney stone formation. Because of the small number of experiments performed here, results must be confirmed by more extensive studies with larger sample size.

Base Sequence↗
PubMed2002

Aggregation and dispersion characteristics of calcium oxalate monohydrate: effect of urinary species.

In this research, screening and central composite experimental designs are used to determine the effect of various factors on the aggregation and dispersion characteristics of previously grown calcium oxalate monohydrate (COM) crystals in artificial urinary environments of controlled variables. The variables examined are pH and calcium, oxalate, pyrophosphate, citrate, and protein concentrations in ultrapure water and artificial urine. Optical density measurements, particle size analysis, optical microscopy, AFM force measurements, and protein adsorption have been used to assess the state of aggregation and dispersion of the COM crystals and to elucidate the mechanisms involved in such a complex system. The data indicate that our model protein, mucin, acts as a dispersant. This is attributed to steric hindrance resulting from the adsorbed mucoprotein. Oxalate, however, promotes aggregation. Interesting interactions between protein and oxalate along with protein and citrate are observed. Such interactions (synergistic or antagonistic) are found to depend on the concentrations of these species. Surface responses for these interactions are presented and discussed in this paper. In summary, solution, surface, and interface chemistries interact in a complex manner in the physiological environment to either inhibit or promote aggregation, and an understanding of such interactions may help determine and control the factors affecting kidney stone formation.

Adsorption↗
PubMed2002

Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants.

In a previous study we demonstrated that oxalate induced free radical injury can promote calcium oxalate stone formation. In the present study, we tested whether the antioxidants vitamin E, superoxide dismutase (SOD), catalase and desferoxamine (DFO) can provide protection against oxalate toxicity in LLC-PK(1) cells. LLC-PK(1) cells were exposed to oxalate (1.0 mM) or oxalate+calcium oxalate monohydrate crystals (COM, 500 microg) for 3, 6, and 9 h. Cellular injury was assessed by lactate dehydrogenase (LDH) release. Malondialdehyde (MDA) content, catalase and glutathione peroxidase activities were also measured. The effect of vitamin E (200 microM), DFO (1.0 mM), SOD (400 U), and catalase (400 U) on oxalate-exposed cells was tested. LLC-PK(1) cells exposed to oxalate showed a significant increase in LDH release and MDA content, which was further elevated when COM crystals were added. Cellular glutathione peroxidase and catalase activities were decreased on exposure to oxalate. The addition of vitamin E, SOD, catalase and DFO significantly reduced the release of LDH and restored glutathione peroxidase and catalase activities towards the control level. The increased formation of MDA on oxalate or oxalate+COM toxicity was restored towards normalization by antioxidants and antioxidant enzymes. The protection rendered by vitamin E was greater than that of SOD, catalase and DFO. We conclude that oxalate associated free radical injury may promote stone formation by providing cellular debris for crystal nucleation and aggregation and augment crystal attachment to other tubular cells. Antioxidant administration may prevent calcium oxalate nucleation and retention in the renal tubules by preventing oxalate mediated peroxidative injury.

Animals↗
PubMed2002

A 5-fluorodeoxyuridine prodrug as targeted therapy for prostate cancer.

A method for targeted delivery of the cytotoxic agent 5-fluorodeoxyuridine (FudR) (1) to sites of metastatic prostate cancer is described. The prodrug was synthesized by coupling the active drug (FudR) to the PSA-peptide via a self-cleaving diamino acid linker to produce HSSKLQ-Leu-Aib-FudR. This prodrug serves as a substrate for prostate specific antigen (PSA). This approach permitted efficient conversion of the inactive prodrug back to the active cytotoxic state by the enzymatic activity of PSA which is highly expressed by prostate cells.

Cell Death↗
PubMed2002

Expression of osteopontin in rat kidneys: induction during ethylene glycol induced calcium oxalate nephrolithiasis.

PURPOSE: Osteopontin is a well-known component of stone matrix and a strong inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals in vitro. To understand its involvement in vivo in calcium oxalate nephrolithiasis we investigated the renal expression and urinary excretion of osteopontin in normal rats, and rats with hyperoxaluria and calcium oxalate crystal deposits in the kidneys. MATERIALS AND METHODS: Calcium oxalate nephrolithiasis was induced by administering ethylene glycol. Immunohistochemistry and in situ hybridization were done to localize osteopontin and osteopontin messenger RNA in the kidneys, while sensitive reverse transcriptase quantitative competitive template polymerase chain reaction was performed to detect and quantify osteopontin messenger RNA expression. Urinary excretion was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis, and then quantified by densitometry of the Western blots. RESULTS: Osteopontin expression in the kidneys was significantly increased after hyperoxaluria and it increased further after the deposition of calcium oxalate crystals in the kidneys. Urinary excretion of osteopontin increased concomitantly. The results reveal differences in renal responses after exposure to oxalate and calcium oxalate crystals. In normal kidneys osteopontin expression was limited to a small number of cells of the thin limbs of the loop of Henle and papillary surface epithelium. During hyperoxaluria osteopontin expression in the kidneys was increased but still mostly limited to cells of the thin limb and papillary surface epithelium. However, after calcium oxalate crystal deposition osteopontin expression was observed throughout the kidneys, including segments of the proximal tubules. CONCLUSIONS: In response to exposure to oxalate and calcium oxalate crystals renal epithelial cells increase the production of osteopontin, which may have a significant role in calcium oxalate nephrolithiasis.

Animals↗
PubMed2002

Oxalate ions and calcium oxalate crystals stimulate MCP-1 expression by renal epithelial cells.

BACKGROUND: Crystals of calcium oxalate monohydrate (COM) and excess oxalate ions (OX) stimulate an array of responses inducing localized injury and inflammation in the kidneys. These inflammatory responses are key regulators of development of nephrolithiasis. We propose that monocyte chemoattractant protein-1 (MCP-1), a chemokine with potent chemotactic activity for monocytes/macrophages, is a mediator of local inflammatory responses to COM and OX-induced injury. To test this hypothesis, the effects of COM and OX on the expression of MCP-1 mRNA and protein by NRK52E rat renal tubular cells were investigated. METHODS: Confluent cultures of NRK52E cells were exposed to COM (33 to 267 microg/cm2) or OX (125 to 1000 micromol/L, estimated free oxalate levels of 65.8 to 540 micromol/L) and catalase (400 or 2000 U/mL), a free radical scavenger that protects the cells against detrimental effects of COM and OX, for 1 to 48 hours under serum free conditions. The conditioned media were collected and total cellular RNA isolated from the cells and subjected to enzyme-linked immunosorbent assay (ELISA) and semiquantitative polymerase chain reaction (PCR) to determine the expression of MCP-1 protein and mRNA, respectively. RESULTS: NRK52E cells express MCP-1 mRNA and protein, and the level of their expression significantly increases following treatments with COM and OX in a time and concentration dependent manner. MCP-1 mRNA expression and protein production increased more significantly after exposure to COM than to OX. These responses were significantly reduced following treatments with catalase (2000 U/mL). CONCLUSIONS: NRK52E cells express MCP-1 mRNA and protein, and their levels are altered following COM and OX exposure. Since catalase treatment reduced MCP-1 expression, free radicals may be involved in the up-regulation of MCP-1 production by the epithelial cells. The results suggest that elevated expression of MCP-1, which is often associated with local inflammatory response, may mediate similar reactions including attraction of macrophages seen around the interstitial crystals during the early stages of nephrolithiasis.

Animals↗
PubMed2002

Presence of lipids in urine, crystals and stones: implications for the formation of kidney stones.

BACKGROUND: Cell membranes and their lipids play critical roles in calcification. Specific membrane phospholipids promote the formation of calcium phosphate and become a part of the organic matrix of growing calcification. We propose that membrane lipids also promote the formation of calcium oxalate (CaOx) and calcium phosphate (CaP) containing kidney stones, and become a part of their stone matrix. METHODS: Human urine, crystals of CaOx and CaP produced in the urine of healthy individuals, and urinary stones containing struvite, uric acid, CaOx and CaP crystals for the presence of membrane lipids were analyzed. Crystallization of CaOx monohydrate at Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidylglycerol (DOPG), palmitoyloleoylphosphatidylglycerol (POPG) and dimyristoylphosphatidylglycerol (DMPG) was investigated to directly demonstrate that phospholipid assemblies can catalyze CaOx nucleation. RESULTS: Urine as well as CaOx and CaP crystals made in the urine and various types of urinary stones investigated contained some lipids. Urine of both CaOx and uric acid stone formers contained significantly more cholesterol, cholesterol ester and triglycerides than urine of healthy subjects. However, urine of CaOx stone formers contained more acidic phospholipids. The organic matrix of calcific stones contained significantly more acidic and complexed phospholipids than uric acid and struvite stones. For each Langmuir monolayer precipitation was heterogeneous and selective with respect to the orientation and morphology of the CaOx crystals. Crystals were predominantly monohydrate, and most often grew singly with the calcium rich (10-1) face toward the monolayer. The number of crystals/mm2 decreased in the order DPPG> DPPC and was inversely proportional to surface pressure and mean molecular area/molecule. CONCLUSIONS: Stone forming conditions in the kidneys greatly impact their epithelial cells producing significant differences in the urinary lipids between healthy and stone forming individuals. Altered membrane lipids promote face selective nucleation and retention of calcium oxalate crystals, and in the process become a part of the growing crystals and stones.

1,2-Dipalmitoylphosphatidylcholine↗