Tomb next to tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tombstones; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Nehemias Dreifus; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tombstone; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Gutele Wormser; Hochberg Jewish Cemetery Cemeteries; Tombs

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Tomb of Salomon Pappenheimer; Hochberg Jewish Cemetery Cemeteries; Tombs

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Jewish refugees from Warsaw waiting at the border train station for transport to Germany Portraits; Groups

Weltkrieg 1914/18 Aus Warschau gefluechtete Juden, die auf einem Grenzbahnhof auf Abtransport nach Deutschland warten

Fritz Gottschalk and his children boating on a mountain lake; Titisee, Germany.

From left to right: Ursula, Walter, Hal, Kurt, Fritz, and Elizabeth Gottschalk; the lake is probably the Titisee near the Swiss border in the Black Forest, Germany

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.

Kurt and Hans Ludwig (Hal) Gottschalk on "skateboards" in front of Kurhaus Brunig; Norderney, Germany. Portraits Children

Left: Kurt Gottschalk; right: Hans Ludwig (Hal) Gottschalk

The six Gottschalk children Ursula, Elizabeth, Hal, Kurt, Freddy and Walter seated in a Strandkorb (roofed wicker beach chair); Nordeney, Germany. Portraits Children

Front row Walter (left) and Freddy; middle row Kurt (left) and Hal; back row Ursula (left) and Elizabeth

The six Gottschalk children Kurt, Walter, Elizabeth, Freddy, Ursula and Hal in the water on the beach; Nordeney, Germany.

From left to right: Kurt, Walter, Elizabeth, Freddy, Ursula and Hal Gottschalk

Jewish cemetery; Hannover, Germany. Cemeteries

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Tombstone on the Old Jewish Cemetery; Hannover Cemeteries

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Tombstone of the Benno Molling family in the Jewish cemetery An der Strangriede; Hannover, Germany. Cemeteries; Tombs

This family grave is next to the tombstone of Adolf Molling and his wife Henriette (Henny) nee Meyerhof